n503f.5-9!
Membrane Domain-ADHESIVE interactions (L5S35)
(1) LATERAL Cell-Cell Adhesive Interactions: **Junctional complexes 1. zonula occulens - tight junctions 2. zonula adherens - adhering junctions 3. macula adherens - desmosomes **Communicating junctions - gap junctions (2) BASAL Cell-Matrix Adhesive Interactions: **hemidesmosomes - half desmosomes **Focal adhesions (3) APICAL Cell-Cell Adhesive Interactions: **Transient binding (selectins) - margination
Describe the structure of each CELL-MATRIX junction/interaction, including its molecular components, organization, location and interactions with other cellular components (cytoskeleton, organelles).
(A) ANCHORING junctions: 1) Hemidesmosome: -attach by: intermediate filaments Attach the basal cell membrane to the basal lamina Involved in stabile, long-term attachments Site of keratin tonofilament (IF) attachment Bind to molecules in the basal lamina: •Laminin •Type IV collagen -Mediated by: integral membrane proteins called integrins (B) Focal adhesion: -attach by: actin filaments Attach the basal cell membrane to the basal lamina dynamic, transient attachments found in many cell types such as: epithelial cells, fibroblasts, smooth muscle immune cells -Mediated by: integral membrane proteins called integrins --Integrins recognize the R-G-D sequence motif (in fibronectin, laminin, vitronectin)-- --Analog of Integrin in muscle: Dystrophin Glycoprotein Complex (binds cytoskeleton of muscle cells to external lamina)
Describe the structure of each adhesive CELL-CELL junction, including its molecular components, organization, location and interactions with other cellular components (cytoskeleton, organelles). (L5S37)
(A) TIGHT junctions: *zonula OCCULENS -attach by: actin filaments Most apically located Encircle the cell circumference Formed by numerous membrane fusions Prevents PARACELLULAR pathway of transepithelial transport -Mediated by: claudins, occludin, JAMs, Tricellulin (B) ANCHORING junctions: 1) Adherens: *zonula ADHERENS -attach by: actin filaments Encircle the cell circumference basal to the zonula occludens 15-20 nm between adjacent plasma membranes -Mediated by: cadherin 1. extracellular domains interact 2. intracellular domains are linked to actin cytoskeleton via catenins --E-cadherin mediates Ca2+-dependent adhesion-- Ex: Cancer: epithelial cells change conformation-> lower Cadherin prod, separate/lose their junctions-> get through/penetrate in other places aka metastasis 2)Desmosomes: *macula ADHERENS -attach by: intermediate filaments Located basal to the belt junctions (occludens and adherens) distributed randomly along the lateral membrane domain strong spot adhesions. -Mediated by: cadherin; paired thickened membrane regions called attachment plaques (desmoplakins and pakoglobins~ homophillic), dense band (desmoglein~ cadherins)) in the intercellular space --Site of intermediate filament (cytokeratin) insertion-- (C) GAP junctions: -communicating -attach: via adapters to other junctions Located randomly along lateral membranes Comprised of packed connexons on adjacent cell membranes, a narrow (2-3 nm) intercellular cleft -Mediated by: integral membrane proteins called connexins
List the principal types of cell junctions that mediate CELL-CELL adhesion and describe the FUNCTION of each.
(A) TIGHT junctions: compartmentalize the integral membrane proteins into apical and basolateral domains Prevent free flow of water soluble molecules between cells (apical ↔ basal). (B) ANCHORING junctions: 1) Adherens: cell adhesion, link actin cytoskeletons of adjacent cells 2)Desmosomes: provide strong spot Adhesions between cells. (C) GAP junctions: provide rapid exchange of small molecules between adjacent epithelial cells ___________________ Mediated by the following CAMs: 1.IgSF CAMs, 2.Cadherins 3.Selectins 4.Integrins (sometimes) permanent-> Junctions transient (selectins)-> Margination
What is CENTROSOME DISJUNCTION?
(CENTRIOLES SPLIT and each centriole pair migrates to OPPOSITE sides) is triggered by mitotic CDKs;
Learn about the LINEAGE TRACING STUDIES of stem cells.
*Lineage-tracing studies show that the Lgr5+cells at the base of crypts are the intestinal stem cells* INTESTINAL -Wntsignaling plays a critical role in the intestinal stem cell niche. -Lgr5 ( a G protein coupled receptor) induced by Wntsignaling *One day after tamoxifenadministration, the only cells expressing β-galactosidase were the Lgr5-expressing intestinal stem cells at the base of the crypts*. After five days, additional blue cells -the epithelial descendents of the intestinal stem cells-were seen migrating up the sides of the villi. Show that the Lgr5+ cells at the base of crypts are the intestinal stem cells. Tamoxifen acitvates Er-Cre chimera to go into nucleus. Er-Cre chimera removes blocking segment of Dna Bgalactosidase is expressed in all descents of cell.
To understand the TRANSCRIPTIONAL NETWORK regulating PLURIPOTENCY of ES cells.
*Oct4, Sox2 and Nanog* ACTIVATE genes for self-renewal, pluripotency REPRESS genes that induce specific differentiation pathways
List the principal types of cell junctions/interactions that mediate CELL-MATRIX adhesion and describe the FUNCTION of each.
*basal (A) ANCHORING junctions: 1) Hemidesmosome: link the cell cytoskeleton to the extracellular matrix, providing adhesion, traction and bidirectional signaling. (B) Focal adhesion: Attach the basal cell membrane to the basal lamina, dynamic, transient attachments.Shape, signaling, force transmission, cell movement ________________ Mediated by the following CAMs: 1.Integrins permanent-> Hemidesmosomes transient-> Cell Migration **Some of the components of ECM important in Cell-ECM adhesion: 1.Collagens 2.Structural/adhesive glycoproteins a. fibronectin b. laminin c. chondronectin d. osteonectin •Have binding sites for both cells and other ECM components (act as x-links) • Function in cell adhesion, migration and *signaling*
What is CHROMOSOME CONDENSATION?
- DNA to be COMPACTED into DNA "travel-friendly" structures; sister chromatid resolution - untangling the intertwined sister chromatids; CONDENSIN COMPLEX - create intrachromosomal linkages that PACKAGE CHROMOSOMES into the characteristic loops seen by EM; CDKs trigger the process by ACTIVATING condensins.
Describe how cells know whether SISTER KINETOCHORES are properly attached to the mitotic spindle.
-"sensing mechanism" - kinetochores that are NOT UNDER TENSION; corrects the wrong attachment; - cohesins, Aurora B and chromosomal passenger complex (CPC) ; - once all chromosomes are amphitelic attached, the cohesin complex is severed and anaphase chromosome segregation is initiated.
ASYMETRIC way of stem cell division.
-Asymmetry by LOCAL DETERMINANTS on one side or asymmetry by going to close PROXIMITY of STEM CELL NICHE cells. -The par (partition) proteins dictate asymetry in early division of cell. Par3, Par6, aPKC on anterior complex. Par1 & Par2 on posterior of cell. -Neuroblasts divide asymmetrically to generate neurons and glial cells in the CNS. The neuroblast sits on top of the smaller ganglian mother cell.
Name 2 modern approaches to study PROTEIN TRANSPORT along the secretory pathway.
-Fluorescence microscopy of cells producing a GFP-tagged membrane protein: see the protein moving from ER to golgi to plasma membrane -sensitivity to cleave by endoglycosidase D: modifications of carbohydrate side chains that occur at different stages of the secretory pathway.
To know about the STEM CELL REGENERATIVE therapy
-Once have sc population identified, you will differentiate in vitro and then inject. -This is the problem because you have partial stemness and partial differentiated. -Must trace stem cell proliferation once engrafted to be sure they are not undergoing any tumorgenic transformation. -Still difficult to determine how many cells to inject.
What is receptor-mediated endocytosis?
-a specific receptor on the cell surface binds tightly to an extracellular macromolecular ligand that it recognizes; The plasma membrane region containing the receptor-ligand complex then buds inward and pinches off, becoming a transport vesicle; *low density lipoprotein (LDL), transferrin, protein hormones, glycoproteins* -RME of such ligands occurs via clathrin/AP2-coated pits and vesicles.
What is the functional definition of START?
-a stage in *G1* after which cells are irreversibly COMMITTED to cell cycle; -G1/S phase CDK activity reaches levels sufficient to INITIATE S phase.
What is the function of the MITOTIC SPINDLE?
-made of microtubules that attach to chromosomes via specialized proteins called kinetochores; -organized by centrosomes (spindle pole bodies) containing g-tubulin; -functions to SEGREGATE CHROMOSOMES so that the sister chromatids separate from each other and are moved to opposite poles of the mitotic spindle;
Explain how CDK ACTIVITY is modulated by CAK, Wee1, Cdc25.
-require an activating subunit to be active -mammalian cells contain 9 CDKs -CDKs bind to different cyclins to promote cell cycle transitions (CDK4/6 - G1 cyclins; CDK2 - G1/S phase and S phase; CDK1 is a mitotic CDK); -cyclins determine the substrate specificity of the complex; -activating and inhibitory phosphorylation; CAK kinase: ACTIVATES Phosphorylation of a THREONINE residue near the active site of the enzyme is required for Cdk activity; CAK activity is CONSTANT throughout the cell cycle; Weel kinase:INHIBITS by phopsphorylating and deactivating the cyclin-CDK complex. Cdc25 phosphatase:ACTIVATES removes phosphates from mitotic cyclin- CDK complex
Define the ER to cis-Golgi ANTEROGRADE and RETROGRADE TRANSPORT. (L8S21)
1 -3. ANTEROGRADE transport ER to cis-Golgi is mediated by COPII vesicles. v-SNARE and cargo proteins in the ER membrane are incorporated into the vesicles by interacting with coat proteins. Soluble cargo proteins are recruited by binding to appropriate receptors in the membrane of budding vesicles. COPII vesicle is released from the ER membrane. The COPII coat dissociates and thus v-SNARE proteins are exposed on the surface of the vesicle. The vesicle is tethered to the cis-Golgi membrane in a Rab-dependent process. v-SNARE/cognate t-SNARE complex assembles in the Golgi membrane allowing membrane fusion to occur. The cargo is released in the Golgi compartment. 4 - 6. RETROGRADE transport cis-Golgi to ER is mediated by COPI vesicles. Membrane bilayer, v-SNARE proteins and missorted ER-resident proteins return from the cis-Golgi to ER.
Describe the VESICLE DOCKING AND FUSION with the target membrane. (L8S19)
1. A Rab protein tethered via a lipid anchor to a secretory vesicle binds an effector protein complex on the plasma membrane, docking the transport vesicles to the appropriate target membrane; 2. A v-SNARE protein (VAMP) interacts with the cytosolic domains of the cognate t SNARE (syntaxin, SNAP-25) and form a very stable vSNARE/t-SNARE complex hold the vesicle close to the target membrane. 3. The two membranes undergo fusion (mechanism not well understood). 4. NSF and a-SNAP bind to the SNARE complex. NSF (ATPase) hydrolyzes ATP to ADP, and drives dissociation of the SNARE complex. SNARE proteins are freed for another round of membrane fusion. Rab-GTP is hydrolyzed to Rab-GDP and dissociates from the Rab effector.
Name the 4 basic TISSUE TYPES that comprise the human body and list their distinguishing characteristics.
1. Epithelial · Line or cover organ surfaces (inside blood vessel) · Regulate transport of materials · Form glands (endocrine, exocrine) · Sheets of cells that may be flat or folded into pleats, tubes, spheres etc. · Adjacent cells are directly attached to one another and have a top (apical) and bottom (basal) surface 2.Connective · Tissues formed by a combination of cells and an extracellular matrix · Forms skeletal structures (bones, ligaments, tendons) · Provide conduit for blood vessels and nerves · Make attachment and support structure · Fill in spaces and provide cushioning (adipose) *lots of ECM* 3.Muscle · contraction · 3 types: **Skeletal · Attached to the skeleton for body movement · Voluntary, striated **Smooth · Component of many organs (skin, stomach, intestines, blood vessels, uterus) · Have no control over - ex: bladder contraction **Cardiac · Muscle forming the walls of the heart chambers (also striated) 4.Nerve • transmission of electrical signals which regulate brain function, muscle and gland activity •Two major cell types **Neurons - cells that generate and receive electrical signals **Glia - mixed population of cells that provide metabolic and structural support to neurons
Describe the events illustrated by the diagram below: (L8S16)
1. Sec 12 a GEF for Sar1 causes GDP - GTP exchange. GTP-Sar1 undergoes a conformational change exposing the Nterminal and becomes tethered in the ER membrane 2. Sar1-GTP drives polymerization of Sec23/Sec24 COPII coat subunits and leads to formation of vesicle buds 3. COPII vesicles are released and GTP is hydrolyzed to GDP 4. COPII coat dissembles. *Coated vesicles accumulate during in vitro budding reactions in the presence of a nonhydrolyzable analog of GTP.*
Describe the sorting of proteins destined for the apical and basolateral plasma membranes of polarized cells.
Different types of vesicles distinguishable by protein components.: a)Direct apical or basolateral sorting - different types of vesicles distinguishable by protein components (Rab, SNAREs); b)GPI-anchor - the only apical-"sorting signal" identified so far; c)Basolateral sorting for all PM proteins (hepatocytes); apically destined proteins are endocytosed and moved to the apical PM by transcytosis.
1.Know the basic types of membrane proteins.
1. Transmembrane Proteins 2. Integral Proteins 3. Peripheral proteins
What is the destination of proteins that reach the trans-Golgi network?
1. trans-Golgi (retrograde transport via COPI vesicles); 2 -3. late endosomes and lysosomes (clathrin-coated vesicles and adapter protein complexes-coated); cell surface (constitutive and regulated secretory vesicles whose coat is not yet characterized).
Describe the difference between HOMOphilic and HETEROphilic CAM interactions.
1.Homophilic binding: two molecules of the same kind (Cadherins, Ig CAM) 2.Heterophilic binding: two different molecules (Integrins, Selectins)
8.What determines the absolute and relative refractory periods.
Absolute refractory period is when a cell cannot be fired again because all of the Na+ gates are in a closed and not ready state. Relative refractory period is when an excitable cell needs increased perturbation to be fired because only some of the Na+ channels are in the closed and ready state
5.Know the difference and practical aspects of active transport vs. facilitated diffusion. Know how the Na+/K+ ATPase works as well as the ABC cassette p-glycoprotein works. Know the drugs that inhibit them.
Active transport moves ions against a concentration gradient. They take energy from the cleave of ATP to ADP and cause a tertiary structural change in the transporter that moves a molecule up a concentration gradient. Moves 3 molecules Na out of cell and 2 molecules of K into the cell. This creates an electrical difference across the membrane. Oubain and Digoxin will reduce the electrical difference ABC standards for ATPase binding cassette. These are MDR pumps. The ABC cassette pumps are a large family of pumps that have hydrophobic (lipophillic) substance. They prevent xenobiotics from entering the cell
Define the term, Cell Adhesion Molecule (CAM) including its typical location and function.
CAMs are proteins located on the cell surface (plasma membrane) involved in binding •Typically transmembrane receptors (integral membrane proteins) •Bind to molecules from adjacent cells or from the extra cellular matrix (ECM) can have two kinds of molecular interactions: 1. Lateral, intracellular, cis - forms dimers, oligomers or clusters within a cell membrane 2.Adhesive, intercellular, trans - forms a binding point between two adjacent cell membranes --cell adhesion molecules help cells stick to each other and to their surroundings.
Name the main types of COATED VESICLES involved in PROTEIN TRAFFICING. Indicate the role of the vesicle coat.
COPII : ER to cis-golgi. Associated GTPase = Sar1 COP1: cis-golgi to ER. Associated GTPase = ARF --Sar1 and ARF belong to the GTPase superfamily of switch proteins that cycle between GTP and GDP-bound forms and control the assembly of vesicle coat.
List the major ADHESIVE interactions cells may participate in with each other and their matrix.
Cell-Cell Junctions •Junctions that provide a barrier •Junctions that hold cells together •Junctions that link the cytoskeleton of adjacent cells •Junctions that allow intracellular movement of small molecules Cell-Matrix Interactions • Adhesions that attach cells to their extracellular matrix, either permanently or transiently
Describe the main steps involved in VESICLE BUDDING and released from the plasma membrane.
Clathrin-coated vesicles bud from the golgi on the outward secretory pathway and from the plasma membrane on the inward endocytic pathway. Clathrin molecules assemble on the cytosolic surface of the membrane - this starts the shaping of the membrane into a vesicle. A small GTP-binding protein DYNAMIN - forms a ring around the neck. GTP is hydrolized, the ring constricts, pinching off the neck and releasing the vesicle.
16.Be able to describe why MS, Guillain Barre, and MG occur.
Diseases attack myelin. The nerve becomes de-myelinated, the Na+ channels spread out over the neuron because not induced by the surrounding myelin. Left with cable properties of neuron to pass electrical signal across the membrane
The Rb PROTEIN has been called the "MASTER BRAKE" of the CELL CYCLE. Describe how the Rb protein acts as a cell cycle brake. How is the brake released in mid- to late G1 to allow the cell to proceed to the S phase?
E2Fs are held INACTIVE through their association with the Rb protein (retinoblastoma) G1 phase CDKs ACTIVATE E2Fs by phosphorylating and inactivating Rb E2Fs then activates genes involved in DNA synthesis cell proliferation is controlled by the presence of growth promoting factors (mitogens) and growth inhibitory factors (anti-mitogens)
Explain the concept of electrical and metabolic coupling of cells via GAP junctions.
Electrical- electrical current by the movement of inorganic salts. If the cells are coupled, they will share this electrical current, allowing the synchronous contraction of all the cells in the tissue. This coupling function requires the regulation of molecular traffic through the gaps. Metabolic-in tissues that are not electrically active. In these tissues, the junctions allow nutrients and waste products to travel throughout the tissue. Coupled cells undergoing development together to become a specialized tissue
Explain the formation of multivesicular bodies.
Endocytosed proteins and vesicles loaded with lysosomal enzymes from trans-golgi network fuse with the late endosomes transferring their cargo. Proteins to be degraded are incorporated into vesicles that bud in the inside of the late endosomes and form a multivesicular endosome. - a single monoubiquitin molecule tags proteins for entry into the multivesicular endosomes; Hrs (Ub-tagged peripheral membrane protein) facilitates recruitment of the endosomal sorting complexes required for transport (ESCRT); - ESCRT proteins act to drive vesicle budding directed into the interior of the endosome as well as loading of specific monoUb-proteins into the vesicle buds. - ESCTR proteins pinch off the vesicle; the vesicle and its cargo are released inside of the endosome; the ATPase Vps4 facilitates the disassembly of the ESCRT complex;
13.Be able to describe the difference between EPSE and IPSE.
Exctitatory postsynaptic potential and inhibitory postsynaptic potential
What are INDUCED PLURIPOTENT stem cells?
Stem cells that have been REPROGRAMMED BACK into a pluripotent stem cell state. *Add Sox factors* to differentiated cells and can reprogram them back into stem cells.
12.Understand the difference between graded potentials and all or none potentials.
Graded potentials are depolarizations that do not reach adequate voltage change (threshold potential) to activate voltage gated Na+ channels. terminal bouton. OR the density of the channels is inadequate to produce sufficient Na+ flux (gNa+) to reach threshold. all or none: The strength by which a nerve or muscle fiber responds to stimulus is independent of the strength of the stimulus. This occurs in the axon hillock
HEMATOPOIETIC STEM CELLS in the bone marrow.
If they can be regenerated you can isolate HSC and you can REGENERATE every BLOOD cell type. Producing many cell types and if you lose stemness you restricted in type of blood cells that can be created. --------------------------- Tissue stem cells •often known as adult stem cells •also includes stem cells isolated from fetal and cord blood •reside in most tissues of the body where they are involved in repair and replacement
3.Understand the partition coefficient (K), what it means, and how it affects transport of molecules.
K; Partition Coefficient Higher K = faster diffusion More hydrocarbon Rich the Higher the K K > 1 more lipid soluble K < 1 more water soluble
What is the role of KDEL and M6P sorting signals?
KDEL -in cis-golgi network and in both COPII and COPI vesicles binds proteins bearing the KDEL sorting signal to return them back to the ER -ER-resident luminal proteins bears a C-terminal KDEL (Lys-Asp-Glu-Leu) sequence that allows them to be retrieved from cis-Golgi to ER. -located mainly in the cis-Golgi network and in both COPII and COPI vesicles binds proteins bearing the KDEL sorting signal and returns them to the ER. M6P - sorting signal (carbohydrate residues) that directs soluble lysosomal enzymes from the trans-Golgi network to the late endosomes. - generated in cis-Golgi, by two Golgi resident enzymes: N-acetylglucosamine phosphotransferase (step 1) phosphodiesterase (step 2) !!! The addition and initial processing of one or more preformed N-linked oligosaccharides precursors Man8(GlcNAc)2 - in the ER is the same for lysosomal enzymes and membrane and secreted proteins.
C-terminal 24 amino acids of Pseudomonas toxin B subunit KEQAISALPD YASQPGKPPR KDEL; C-terminal 24 amino acids of Shiga toxin B subunit TGMTVTIKTN ACHNGGGFSE VIFR; From inspection of these sequences, what is the probable targeting receptor for transfer of Pseudomonas toxins from the Golgi apparatus to the ER?
KDEL: KDEL receptor in cis-golgi network and in both COPII and COPI vesicles binds proteins bearing the KDEL sorting signal to return them back to the ER -binding affinity of KDEL is sensitive to pH The pH of the Golgi compartment favors binding of the KDEL-bearing proteins to the KDEL receptor in Golgi-derived vesicles and thus their return to ER.
Describe the endocytic pathway of: A. LDL B. transferrin
LDL - 839 aa residues glycoprotein with a single transmembrane segment; - short C-terminal cytosolic segment and a long N-terminal exoplasmic segment that contains the LDL-binding domain; (seven Cys-rich repeats bind the ApoB LDL Receptor molecule in the LDL particle) - the cytosolic segment contains the sorting signal of the LDLR , so the receptor-ligand complex is incorporated into endocytic vesicles; - internalized LDL particles - lysosomes (proteases & cholesteryl esterases); - mutations in the LDLR gene - familial hypercholesterolemia; *Acidic pH= receptor ligand complex dissociate TRANSFERRIN '- major glycoprotein in the blood, transports iron to all tissue cells; - apotransferrin -iron free form -binds 2 Fe3+ ions tightly to form ferrotransferrin; - transferrin-R, on the cell surface binds ferrotransferrin at neutral pH; - transferrin-R/ferrotansferrin complex is endocytosed → late endosomes (pH ~5); - apotransferrin remains bound to the receptor; Fe3+ ions dissociate, are reduced to Fe2+ and remain in the cell; - apotransferrin → returns to the cell surface → secreted; at neutral pH it dissociate from receptor
2.Recognize that there are special regions of membranes called lipid rafts and that they create special environments for transporters and receptors.
Lipid rafts are specialized membrane domains enriched in certain lipids cholesterol and proteins. Caveolae are flask shaped invaginations on the cell surface that are a type of membrane raft. -regulating the expression of receptors and transporters by participating in the control of "how many" receptors and transporters are present on the surface of cells
Stem cell NICHE.
Location of stem cell where you can maintain its stemness. If cell removed from location, the stemness will go down or potentially completely abolish. Type B neural stem cell need ependymal cells, astrocytes, neuroblasts and neural progenitor cells to maintain stemness.
To understand how each CELL CYCLE stage is induced and controlled.
M CHECK: Spindle assembly check point - Chromosomes attachment to spindle G1 CHECK: - Cell size - Nutrients - Growth factors - DNA Damage !!Carcinogenesis!! G2 CHECK: - cell size - DNA replication
To understand the patterns of STEM CELL DIFFERENTIATION
Maintain stem cell population Increase stem cells Increase differentiating cells Want more symmetric division if trying to increase stem cell population
Describe NUCLEAR ENVELOPE breakdown, the NUCLEAR LAMINA and its regulation by phosphorylation.
NUCLEAR ENVELOPE -double-membrane extension of the endoplasmic reticulum containing nuclear pore complexes -Mitotic CDKs PROMOTE nuclear membrane BREAKDOWN NUCLEAR LAMINA -The lipid bilayer of the inner nuclear membrane; meshwork of lamin filaments; Mitotic CDKs PHOSPHORYLATE lamins → DESINTEGRATION of nuclear lamina Mitotic CDKs phosphorylate nucleoporins;
10.Understand the difference and similarities between osmotic and oncotic pressure.
Oncotic pressure, or colloid osmotic pressure, is a form of osmotic pressure exerted by proteins, notably albumin, in a blood vessel's plasma (blood/liquid) that usually tends to pull water into the circulatory system and keep vessels patent Osmotic- Pressure needed to prevent water from moving across a membrane to balance the water concentration
SELF-RENEWAL and DIFFERENTIATION in pluripotent and multipotent stem cells.
SOX changes factors because it is trying to maintain stemness. Changes methylation to either repress or activate histones
Give examples of molecules that can traverse the GAP junctional passage.
Small molecules: glucose, ions, H20, NOT PROTEINS
15.Explain why Na+ channel density is so important in neuronal activity.
Sodium channel density determines threshold. High density and Na+ molecule comes in, more likely to have a minor change in voltage
Inducers of STEM CELL REPROGRAMMING.
Sox2, Klf4, Oct4, c-Myc. Sox factors are inducers of cellular reprogramming.
6.Know how symporters and antiporters and where they derive their energy.
Symporters and antiporters move substances against concentration gradients by taking advantage of a molecule that is moving down its gradient. Na/K ATPase that keeps the Na concentration high in the extracellular space, there would be no concentration gradient to allow for glucose transport. H+ also provides the substrate for the antiporter to extrude H+ while bringing in DA against its gradient.
Describe the general structure of INTEGRINS and explain the concept of COMBINATORIAL diversity.
The combination of one alpha with one beta allows the integrin receptor to bind to different ligands in the matrix & diff pathways generated depending on the binding. Many matrix proteins are recognized by multiple integrins. NOT bound= inactivated BOUND lingand= activated= inside out or outside in signaling
11.Be able to predict if a cell will swell or shrink in hypo and hypertonic solutions and what role aquaporin plays in this and how ADH works.
Thus, a hypotonic solution has less solute outside than inside, while a hypertonic solution has more solute outside than in.
APICAL CELL-CELL adhesive interactions
Transient binding (selectins)- margination Selectins •Mediate leukocyte - vascular cell interactions •Involved in dynamic attachments •Have a Ca2+ -dependent lectin domain •Bind to sugars in glycoproteins Ex: attach cells to blood vessel walls
7.Know how voltage-gated ion channels work, how they function together to create an action potential, be able to label the various elements of the action potential, and know what ion is involved with each phase.
Triggered by concentrations, ligand, voltage, pH, and even oxygen tension. Na+/K+ATPase working to return to polarized state. The cell is deploarized to about -55 mv when the Na+ channels open. When K+ channels open, take K+ from inside of cell and extrude to outside of cell. Taking positive charge away from inside of cell and returning to original polarized cells. (Replorization) Hyperpolarization Resting Membrane Potential Ions move down their concentration based on hydrated radius.
4.Be familiar with the various types of transporters discussed in class and be able to discuss what they do.
Uniporter: always move a substance down a concerntration gradient. Specific and subjuect to inhibition. Symporter: move a solute and ion down their concentration gradients. Cotransporter. Voltage/Ion dependent transporter. (VMAT) Antiporter: move an ion down its concentration gradient to move solute up its gradient (VMAT) Flippase: flip phospholipids from one side of a bilayer to the other area Principle: ATP makes a disproporationate amoutn of ion across a membrane. Ion moves down concentration gradient and that moving down its concentration gradient provides enough energy to move something out or in
What are STEM CELLS?
a cell that is NOT YET SPECIALIZED •the process of specialization is called DIFFERENTIATION •once the differentiation pathway of a stem cell has been decided, it can no longer become another type of cell on its own
Definition of TISSUES
aggregates or groups of cells organized to perform one or more specific functions
What is the process of CISTERNAL MATURATION.
an individual cisterna labeled with the cis-Golgi protein can be seen to progressively loose this protein and acquire the trans-Golgi protein; a process of anterograde transport that depends on resident Golgi enzymes; - secretory cargo proteins acquire carbohydrate modifications in the proper sequential order, without being moved from one cisterna to another by anterograde transport
What makes CELLS into TISSUES?
cohesive and have a means of communication Cohesion: includes adhesion, distribution of force and common function Communication: Includes small molecule exchange, electrical (ionic) coupling and signaling pathways
To understand the Cdks as master regulators of cell cycle progression.
• CDKs are ONLY ACTIVE in the STAGE OF CELL CYCLE they TRIGGER; • Different types of cyclin-CDK complexes initiate different events (G1-phase CDKs, G1/S phase CDKs, S-phase CDKs); • APC/C (anaphase-promoting complex/cyclosome) initiates anaphase and exit from mitosis;
Associate specific clinical conditions with junctional dysfunction or LOSS of ADHESION properties.
•Cell ADHESION or the loss of adhesion is one of the decisive events in CANCER metastasis 1. Integrin signaling Down-regulates E-cadherin disrupts cell-cell adhesion allowing augmented cell motility Upregulates matrix metalloproteinases results in degredation of matrix components (basal lamina) 2. Laminin: abnormal expression promotes migration ------------------------ •JUNCTIONAL (Tight junction) failures pathogenic INFECTIONS or inflammatory effects - loss of the barrier function of epithelial layers (GI and respiratory tracts) •Clostridium perfringens: toxin binds to claudin= not incorporated into tight junction= junctional breakdown •Heliobacter pylori: binds to zonula occludins proteins and translocates one of its own proteins into epithelial cells=cytoskeletal rearrangements= junction failure gastric ulcers! •Leaky Gut syndrome: epithelium breakdown=allows toxins, pathogens, and waste to penetrate the intestinal barrier and reach the vasculature, having systemic effects Parasitic pathogens: •Dust mites: fecal pellets contain peptidases that cleave occluding and ZO-1 protiens -inhaled allergens- asthma ---------------------- •Dermatologic/SKIN blistering conditions due to DESMOSOMAL disruption •Pemphigus vulgaris: autoimmune destruction of demogelins; hemidesmosomes= intact & adhering, desmosomes=NOT adhering to one another •Arrhythmogenic right ventricular dysplasia (a HEART condition) is due to mutant genetic desmosomal protein; components of INTERCALATED DISC= desmosome=not attched to one another=myosite death; cant regenerate=scar tissue; death in cardiac muscle, replaced by fibrous CT and fat
To understand the maintenance and differentiation of EMBRYONIC STEM CELLS.
•Donated excess IVF embryos 1. Isolate inner cell mass of blastocyst. 2.Mix with fibroblast feeder cells which give out factors needed from growth. 3. Isolate dissociated cells. Replate to new feeder cells. Establish ES cell cultures.
Why are STEM CELLS special?
•SELF-RENEW to make more stem cells •DIFFERENTIATE into a specialized cell type Pluripotent= many types of cells (embryonic) Multipotent= a few types of cells (tissue)
