Cell Bio exam 1
Collagen structure
- Fibrils are organized into bundles - some longitudinal and some shown in cross-section - collagen forms a lattice that emits strength
Adherens Junctions Respond to Forces Generated by the Actin Cytoskeleton
- Cell to cell junctions are able to sense increased tension and respond by strengthening their actin linkages -Mechanotransduction - the connection with actin cytoskeletal allows for the responses to change in pressure within cell, (A) so cadherin that isn't attached then it'll be free float, under conditions where the actin filament is pulled (like in mitosis) the actin is pulling the adapter proteins that then exposes binding sites so it allows for more association with actin —> allows for cadherins to attached to the neighboring cells. - pulling on actin allows tension to be transmitted.
glycosaminoglycan (GAG)
- Repeating disaccharide sequence of a heparan sulfate glycosaminoglycan (GAG) chain - highly negative polysaccharide that is used as a matrix - creates a hydrated gel and makes up the connective tissue in organisms - gel with a lot of pressure and reform can resist compression - hydrated molecule of hyaluronan - resist compressive forces in tissues and joints - contain repeating disaccharide units
The structure and function of Selectins
- Selectins mediate transient cell-cell adhesions in the bloodstream (selectins on endothelial cells bind to oligosaccharides on surface of WBC which activate other proteins which enable to WNC to adhere to the vessel wall and then crawl out of the blood vessel) - selectins proteins allow for transient interaction between 2 different types of cells. -selectins important in white blood, it encounters new environment in the epithelial and it wants to go through endothelial cells to convey to tissue and contact the endothelial cells through blood vessels via selective interactions and once it comes to place to specific tissue it wants to go to so it sends a signal to the cell saying you now have to go into this region and to fight infection so stronger interaction used through integrins the stronger interaction would cause cell to push through the gap of the cells - it is like an invasion kind of process.
Types of junctions in vertebrate epithelial cells
- actin-linked cell-matrix junction: - hemidesmosome: - Gap junction: - Desmosomes: - Adherens junction: - tight junction:
Adherens Junctions between epithelial cells in the small intestine
- adherens junction is important in small intestine because you would need to form tight seal to not allow passage of the lumen of the cell to be consumed in the stomach. - adhesion belt is through cells of neighboring cells - in some circumstances, you would need a ring to prevent leakage for lets say blood vessel
ECM
- allows communication between cells - series of proteins and carbohydrates, ECM molecules - is made and oriented by the cells within it - cell creates polysaccharides and collagen that surrounds it so protecting from the environment - different type of collagen forming fibrils in the ECM polysaccharides (GAG) proteins polysaccharides and proteins = glycoproteins protoglycagn = protein + sugar
actin-linked cell-matrix junction:
- anchors actin filaments in cell to ECM - integrin protein
hemidesmosome:
- anchors intermediate filaments to extracellular matrix - alpha, beta, integrin, type 17 collagen
Basal Lamina function in regeneration
- basal laminin is a physical structure that acts a solid support. It is easier to break the ECM than basal lamina - basal laminin can indicate where the cell is and where the cell dies; it can disconnect to its neighbors - basal laminin leaves a footprint of where communicated cells were. - connects axon to muscle cell, under conditions where axon gets cut or muscle cell gets damaged then the connectivity is loss; however,basal lamina says where the cell was and certain structure of cells communicated with - cut muscle cell/ axon the, cell will die off, but basal lamina remains as a template and it can redirect where the cells can grow in this space and redirect where the correct spot where the junction was. - because of specific protein found, this where the nerve should connect and the basal lamina tells where the muscle cell were. - the outside of the cell is important for the function of the tissue
Cadherins structure and function
- cadherin are calcium dependent proteins so the ECM environment has high calcium conc. (needed for cell-cell interaction) - calcium allows conformational change for the protein to bind to each other - cadherin is protein found in plasma membrane, which allows one cell to bind to another cell ( both cells express cadherin prt. then they'll bind)
Members of the Immunoglobulin Superfamily Mediate Ca2+-Independent Cell-Cell Adhesion
- calcium dependent mechanisms for cell-cell adhesion - ICAM - intercellular cell adhesion molecule which means sticking two cells together; resemble antibody structure and shape - red = disulfide linkage - NCAM - neural cell adhesion molecule
Catenins Link Classical Cadherins to the Actin Cytoskeleton
- connect cadherin to actin you would need a scaffold protein or adaptor protein (p 120 catenin, B-catenin, a-catenin) - set of interaction of cystolic prt.
Adherens junction:
- connects actin filaments bundle in one cell with that in the next cell - cadherin proteins
Cadherin-Dependent Cell-Cell Adhesion Guides the Organization of Developing Tissues
- each cell have specific type of cell surface signature - blastula; each color represents each cell type, each cell rearrange itself based cadherin expressed - development of neural tube, overtime you'll express certain cadherins and what would be an ectoderm would associate with each other
Activation of Integrins by intracellular signaling
- example of platet to when it is in blood clot - has thrombin receptor which activates GDP proteins then it activates talin, RIAM, kindlin - bind as an adaptor protein and the integrin bind to ECM protein
Gap Junctions Couple Cells Both Electrically and Metabolically
- gap junction allows for passage of currents and small molecules in neighboring cells - 100 - 1000 daltons - protein are too big to go through the gap junction - 50 daltons = amino acids - blood cell cant go through - gap junction is more like pores not transporter
Integrins - part of a hemidesmosome
- integrins are part of hemidesmosomes ( association of cell with ECM an intermediate filaments) - integrins theres alpha beta dimer it'll bind to collagen 17, associate with laminin and it'll associate with collagen (intermediate) - for communication b/w outside and inside the integrins have particular adapter proteins (plectin/ BP230) allows integrins bind to keratin - adapter protein generated to specific domains in the cytoplasm
Integrins Can Switch Between an Active and an Inactive Conformation (2 states)
- integrins aren't always active - active form to inactive form is due to cell signaling - strong ligand binding would allow strong adaptor protein binding
Integrins Are Transmembrane Heterodimers That Link the Extracellular Matrix to the Cytoskeleton
- intergrins communicates ECM and cytoskeleton of the cell: (would be the communication in both inside of the cell and outside of the cell) - integrins can bind to actin or intermediate filament depending on the structure that is formed, plasma membrane proteins, transmembrane proteins, - 2 different integrins -> heterodimer (dimer of two different peptides and have alpha and beta subunit of integrin) - outside domain (ECM) the of the integrin need specific domain binding to ECM protein (dependent on the type of protein it is= affect the type of integrin you have). - it would associate with the cytoskeletal protein or adapter protein - in this case integrin associate with talin which then associates with vinculin and these associates with actin itself - integrin doesn't physically associate with actin, it would need an adapter molecule. It would respond to change in actin structure - talin adapt molecule can respond to change in actin structure
cytoskeleton
- intermediate filaments are group proteins that form filaments within a cell. - microtubules are made up of proteins known as the tubular - actin filaments made up of protein actin
Transmembrane adhesion proteins link the cytoskeleton to ECM
- junctions are mediated by proteins through plasma membrane - proteins have one domain in the cytoplasm and one domain in the outside of the cell - proteins are integral membrane proteins, attachment to ECM are made by integral membrane proteins that has specific domains inside/outside of the cell - intracellular domain of the protein are associated with the cytoskeletal part of the cell or the signaling molecules for response internally; allows for cells to position itself and grow in the right place.
tight junction:
- seals gap between epithelial cells -
Cadherins form a diverse family of adhesion
- specific type of adaptor proteins - domain structure of cadherins would interact with cadherins of another cell; - homophilic binding : have the affinity for the same molecule that is; for instance E. cadherin binding to E. cadherin ( same molecule interacting with itself - homophilic binding allows for same type of cell that needs to have specific arrangement with certain cells, it can recognize the neighbors it needs to bind to - Heterophilic binding: binding of two different proteins but they have affinity for each other - Heterophilic binding allows for multiple cell types it needs to be attach itself to.
The Basal Lamina (basement membrane) Is a Specialized Form of Extracellular Matrix
- structural and filtering role as well as involved in polarity, metabolism, protein organization in plasma membranes, cell survival, proliferation, differentiation and migration.
Cell-Matrix Adhesions Respond to Mechanical Forces
- talin is similar to fibronectin that can be stretched by physically pulling it - it would expose region by pulling which allows region to be exposed for adaptive protein to bind - talin is compacted form, experimentally it was magnetically attached to the glass slide, with the magnetic you can pull a protein and stretch it, you expose region that was hidden before, allow adaptor proteins to attach; helps cell to response to physical stresses in the cell Talin is a tension sensor at cell-matrix junctions! When actin filaments are pulled by myosin motors inside the cell, the resulting tension stretches Talin, thereby exposing the vinculin binding domain, vinculin binds and recruits additional actin filaments and thereby tension increases the strength of the junction.
Proteoglycans Are Composed of GAG Chains Covalently Linked to a Core Protein
- theres different glycolytic linkage - act like fillers in b/w cells - they fix the gaps - GAG attach to proteins known as proteoglycan - has repeating disaccharide unit attached to specific amino acid of the protein - theres a tertrasaccharide attached to core protein ( in some proteins have serine by hydraulic linkage) - attached to core protein and you have single things coming out of it - some proteins are tiny globular proteins - there are different type of proteoglycans
Desmosomes:
-connects intermediate filaments in one cell to those in the next cell - nonclassical cadherins: desmoglein and desmocollin - epithelial attached to desmosome allows the cell to have physical mechanical strength - nonclassical cadherin type molecules associating with each other; on the intracellular side nonclassical cadherin protein attached to adaptor protein
Fibronectin structure (dimer)
-fibronectin is a glycoprotein in the extracellular matrix - tell if the cell is in the right environment ( cell says i should stay here) - Fibronectin may unfold upon stretching exposing a cryptic binding site that enables other fibronectin molecules to bind resulting in the formation of fibronectin fibrils
Elastin fibers
Elastin - gives tissues (skin, blood vessels, lungs) their elasticity and resilience to recoil after transient stretch - A network of Elastin fibers - similar to a rubber band!
INTERMEDIATE FILAMENTS
Intermediate Filaments Are Strong and Ropelike Intermediate Filaments Strengthen Cells Against Mechanical Stress The Nuclear Envelope Is Supported by a Meshwork of Intermediate Filaments keratin is an example of intermediate filament protein green is keratin ( gene of keratin protein or antibody) mostly in the cytoplasm, very little in the nucleus in epithelial cells- theres need to be a strong connectivity between cells and intermediate filaments in order to keep the cells intact together based on desmosome type structures. desmosomes are where two cells are in contact with each other. usually very difficult thing to break
The role of tight junctions in trancellular transport
Transport proteins are confined to different to different regions of the plasma membrane in epithelial cells of small intestine Tight junction confine the transport proteins to their appropriate membrane domains by acting as diffusion barriers within the lipid bilayer - they also block the backflow of glucose. - junction important because tight junction prevent mixing of fluid of one side of the cell with other side of the cell. - absorb glucose from lumen of the gut and bring inside the cell through transporters so there is a conc, gradient of glucose: low in the lumen, high in cell and low in the blood - transporter need to move glucose from the lumen into the cell to build up high conc. glucose so it can be transported into the blood stream using a different type of transporter - so theres two reasons why tight junctions are important: (1) they provide physical barrier to host ( free passage for glucoses, without it there wouldn't be a conc, gradient of glucose) (2) give cell polarity it would restrict one side of the tight junction (so the green transporter are found in the gut not found int the basal lamina and the red transporter are found in the side of basal lamina) this cause it is expressed one side because the tight junction
Gap junction:
allows the passage of small water soluble molecules from cell to cell ( allow communication b/w neighboring cells)
Basal Lamina function in regeneration prt 2
basal lamina function in regeneration, cells that died off and it needs to be regeneration ECM is dynamic organization outside the cell, ECM can change and give/receive signals. ECM can be degraded by the cell so that it can be used for remodeled, repair cells. ( important for development/ migration) Enzymes that break down proteins: 2 types of proteases that can degrade ECM: metalloprotease, serine proteases matrix metalloprotease depend on Ca2+ and Zn 2+ serine proteases have highly reactive serine in their active site activity confined to plasma membrane theres metalloprotease(generic) that break down any proteases it sees; you highly specific proteases (i.e. collagenases) you don't want this activity to occur often so you want to regulate this activity by only activated when needed activity confined to cell surface by anchoring proteins; production of protease inhibitors (allow control for the activity) cancer cells would produce promote metalloprotease because it allows more replication of cancer cells.
Assembly of a an adherens junction (cadherin/catenin interactions) - link to cytoskeleton
cadherin see each other, the stick around forming homophilic interaction then it'll signal cadherin to come closer —> actin would be recruited—> self propagating event sort like a zipper, it'll form tighter interactions —> form actin bundle of myosin
Cadherin-Dependent Cell-Cell Adhesion - experimental evidence for cell sorting
example of cell sorting based on type of cadherin and the concentration - low level of E- cadherin is on exterior; whereas, high level is toward the center
A Gap-Junction Connexon Is Made of Six Transmembrane Connexin Subunits
gap junctions are physical holes created by certain set of proteins, these proteins are ring like structure form between the two plasma membrane cells protein that makes up the gap junction is a connexin ( subunit for connexons which is made up of 6 monomers) 2 connexon meet at the exterior of the cell specific size determines what can go through
Desmosomes and Hemidesmosomes and the intermediate filament network
keratin are intermediate filaments so protein associated with desmosomes and hemidesmosomes connection with mechanical strength
Tight Junctions Contain Strands of Transmembrane Adhesion Proteins
seal is in between the two cells proteins involved are claudin and occludin arranged interiorly by the cell are called ZO proteins