Cell Junctions & Cell Adhesion

anchoring proteins

proteins that attach the plasma membrane to other structures and stabilize its position

Desmosomes

(anchoring junctions) fasten cells together into strong sheets Anchoring junctions that prevents cells subjected to mechanical stress from being pulled apart; button like thickenings of adjacent plasma membranes connected by fine protein filaments connects intermediate filaments in one cell to those in the next cell

Homophilic Binding Cadherins

(occurs between cells expressing the same receptor; most common intercellular adhesion mechanism) cadherins bind cadherins in presence of sufficient [Ca2+] form zipper-like structures between adjacent cells via homophilic binding to other cadherins in a calcium-dependent manner. Classic cadherins, such as the N-, P-, and E-cadherins, localize in adherence junctions to form an adhesion belt and build a connection with the actin-containing cytoskeleton.

cadherin superfamily

-Cell-cell adhesion -Adherens junctions: cadherin attaches to actin -Desmosomes: cadherin attaches to intermediate filaments. Desmosomes are composed of cadherins that bind to cells together. They associate with intermediate filaments inside the cell to give the cell mechanical strength. -all have a transmembrane region (part interacts with cytosol and the other the extracellular matrix) constitute a superfamily of cell-cell adhesion molecules expressed in many different cell types that are required for proper cellular function and maintenance of tissue architecture. Binding between cadherin extracellular domains is weak, but strong cell-cell adhesion develops during lateral clustering of cadherins by proteins that link the cadherin cytoplasmic domain to the actin cytoskeleton. extracellular domain of classical cadherins in regard to the control of recognition and adhesive contacts between cadherins on opposing cell surfaces.

Channel-forming junctions

-gap junction allows the passage of small water-soluble molecules from cell to cell (ions) usually located below adherens junctions, sometimes/often near basal end regulated by extracellular signals connexins & connexons --- > can be metabolically or electrochemically coupled

Lectin

A large protein family that binds a carbohydrate, commonly an oligosaccharide, with very high affinity and specificity, mediating cell-cell interactions. Ca2+ dependent heterophilic interactions when they bind to glycoproteins

Vinculin

A protein that mediates the association of actin filaments with integrins at focal adhesions.

vinculin

A protein that mediates the association of actin filaments with integrins at focal adhesions.

disulfide bridges

A strong covalent bond formed when the sulfur of one cysteine monomer bonds to the sulfur of another cysteine monomer.

Integrins

A transmembrane protein that interconnects the extracellular matrix and the cytoskeleton. membrane proteins; they transmit signals between the ECM and cytoskeleton

alternative RNA splicing

A type of regulation at the RNA-processing level in which different mRNA molecules are produced from the same primary transcript, depending on which RNA segments are treated as exons and which as introns. Genes giving rise to two or more different polypeptides depending upon which segments are treated as exons. A type of eukaryotic gene regulation at the RNA-processing level in which different mRNA molecules are produced from the same primary transcript, depending on which RNA segments are treated as exons and which as introns.

Desmocollin

A type of transmembrane cadherin that links intermediate filament cytoskeletons of adjacent cells at desmosomes.

desmoglein

A type of transmembrane cadherin that links intermediate filament cytoskeletons of adjacent cells at desmosomes.

Cadherins are indirectly bound to what? via what? what is characteristic of a classical cadherin?

Actin via linking catenin proteins 5 repeat protein domains

Talin

Adaptor protein which competes with the a-subunit of integrin for a binding site on the b-subunit; it mediates the interaction of integrin with actin filaments

intercalated discs

Attachment sites between the transverse lines between cardiac muscle cells specialized connections between myocardial cells containing gap junctions and desmosomes

Cadherin-cadherin interactions are mediated by what?

Cadherin-cadherin interactions are gated by extracellular Ca2+, which serves to rigidify the cadherin extracellular domains and promote trans junctional interactions.

What are the two proteins in tight junctions? how many transmembrane areas? & what kind of bonds ? what protein do these TJ proteins all interact with?

Claudin occludins 4; hydrophobic Actin

EGF like domain

Epidermal Growth Factor; is an evolutionary conserved protein domain, which derives its name from the epidermal growth factor where it was first described. It comprises about 30 to 40 amino-acid residues and has been found in a large number of mostly animal proteins. (growth factors, lipoprotein receptors, selectins, clotting factors, extracellular matrix proteins, etc.) and are frequently seen in tandem repeats with various degrees of conservation.

Integrins wrt WBCs

In animal cells, a transmembrane receptor protein with two subunits that interconnects the extracellular matrix and the cytoskeleton. A transmembrane protein that interconnects the extracellular matrix and the cytoskeleton; maybe biggest adhesion protein in WBCs membrane proteins; they transmit signals between the ECM and cytoskeleton Ca2+ independent (unlike selectins and cadherins) heterophilic binding (with selectins or glycoprotein interactions) : alpha/beta integrins bind ECM proteins, transient interaction

Leukocyte Emigration

Escape of large amount of WBC's into the site of inflammation Escape occurs in post capillary venules ONLY WBC's are actively pushed out, taking about 10 minutes Leukocyte emigration from the vasculature at sites of inflammation is regulated by at least four sequential steps: Endothelial cells and leukocytes are first activated or primed by inflammatory stimuli such as infectious agents and inflammatory cytokines (e.g., TNF-α, IL-1, INF-γ, and IL-8) to increase surface expression of adhesion molecules (e.g., E- and P-selectins, carbohydrate selectin ligands, ICAM-1, VCAM-1, LFA-1, and VLA-4). The initial step of leukocyte-endothelial cell adhesion involves leukocyte margination and "rolling" along the endothelial surface, a low-affinity interaction mediated by the selectins, VLA-4, and their ligands. The second step requires the tethered leukocyte to become activated, a process mediated by chemokines and other chemoattractants.336 These mediators increase integrin adhesiveness by augmented receptor affinity and mobilization of integrin from cellular stores. This ushers in the third stage, in which the rolling leukocyte arrests, spreads, and firmly adheres to the endothelium, mediated by interactions between integrins and immunoglobulin superfamily molecules (e.g., VLA-4/VCAM-1, LFA-1/ICAM-1, and LFA-1/ICAM-2).385 During transendothelial migration—the final step—the leukocyte squeezes in an ameboid fashion between tightly apposed endothelial cells. This interaction involves homotypic interactions between two molecules found both on leukocytes and endothelial intercellular junctions: platelet/endothelial cell adhesion molecule (PECAM)-1, a member of the immunoglobulin gene superfamily, and CD99.4

catenins

Family of proteins which function as adaptors proteins. In adherens junctions and desmosomes, they link cytoskeletal filaments to the intracellular domains of cadherins. link cadherins to the actin cytoskeleton Mediate the Actin-Cadherin Linkage in Cell-Cell Adhesion

Claudins

Form the backbone of tight junctions, charged amino acids in extracellular loop, pores allow passage of certain ions, scaffold binding site

Cell-cell adhesions.

Formed on plasma membranes. Held together by extracellular membrane, cell adhesion molecules, specialized cell junctions. gap junctions, desmosomes, tight junctions allows cells to give rise to tissues / organs intracellular anchor proteins transmembrane adhesion proteins primarily cadherins homophilic binding

NCAM has what kind of interactions?

Homophilic (expressed NCAMs on one cell will bind to expressed NCAMs on another cell) Ca2+ independent

plakoglobin

In desmosomes, they are adaptor proteins that are bound by transmembrane proteins, desmocollin and desmoglein. gamma catenin, major cytoplasmic protein common to submembranous plaques of both desmosomes and intermediate junctions

ICAMs

InterCellular Adhesion Molecules; endothelial , wbcs bind integrins on WBCs

adherens

Joins actin bundles between cells

what is largely responsible for forming a major epithelial tissue permeability barrier/layer?

Occluding junctions/ Tight junctions

epithelial tissue

Sheets of tightly packed cells that line organs and body cavities; most abundant tissue type have basal lamina type IV Collagen

Na+ driven glucose symport

Sodium-glucose Symporter is a transmembrane protein and is an example of sodium-driven Secondary active transport that occurs in the epithelial cells of the small intestines. ... Therefore, the sodium influx from the lumen to the epithelial cell is coupled with glucose transport activity mediates apical sodium and glucose transport across cell membranes. Cotransport is driven by active sodium extrusion by the basolateral sodium/potassium-ATPase, thus facilitating glucose uptake against an intracellular up-hill gradient. Basolaterally, glucose exits the cell through facilitative glucose transporter 2 (GLUT2) [1]. These proteins mediate the active transport of glucose against an electrochemical gradient. Glucose in the intestinal lumen or the nephrons is transported against its concentration gradient by another transport mechanism, where glucose uptake is coupled with the uptake of sodium ions that are also being transported down their concentration gradient.

connexins

The proteins that make up gap junctions (connexons)

connexin

The type of protein found in/make gap junctions proteins that form connexons (channels) about 6 connexin subunits per connexon 20+ different types

Structure and Composition of zonula adherens

The zonula adherens is composed of several different proteins: -The actin microfilaments of the cytoskeleton (the internal skeleton of the cell). -Anchor proteins, found inside each cell. These are called alpha-catenin, beta-catenin, gamma-catenin (aka plakoglobin), vinculin, and alpha-actinin. They link the actin microfilaments to the cadherins. -Cadherins, namely E-cadherin. These are transmembrane adhesion proteins, whose main portions are located in the extracellular space. The extracellular part of one cell's cadherin binds to the extracellular part of the adjacent cell's cadherin in the space between the two cells. Each cell's cadherin molecule also contains a tail that inserts itself inside its respective cell. This intracellular (within the cell) tail then links up to catenin proteins to form the cadherin-catenin complex. This complex binds to vinculin and alpha-actinin; these two proteins are what link the cadherin-catenin complex to the cell's internal skeletal framework (the actin microfilaments). The extracellular portions of the cadherin molecules of adjacent cells are bonded together by calcium ions (or another protein in some cases). This means that the functional as well as morphological integrity of the adherens junctions are calcium dependent. If you were to remove calcium from the equation, this type of cell junction would disintegrate as a result.

occluding junctions key functions

Tight junctions are the closely associated areas of two cells whose membranes join together to form a virtually impermeable barrier to fluid. (layers of epithelial tissues are major permeability layers) Tight junctions perform vital functions—such as holding cells together—and form protective and functional barriers. Tight junctions are composed of a branching network of sealing strands with each strand acting independently from the others. The major types of proteins in junctions are the claudins and the occludins. Each strand is formed from a row of transmembrane proteins embedded in both plasma membranes, with extracellular domains joining one another directly.

Vinculin and Talin

Tong like anchoring proteins

paracellular transport

Transport of materials through the interstitial space without interactions with the cytoplasm or cell membrane through junctions between adjacent cells e.g. movement of sugars/aas.

various cadherins t/f all in table are Ca2+ dependent

True

three major functions of cadherins in cell-cell contact formation and stability.

Two of those functions lead to a decrease in interfacial tension at the forming cell-cell contact, thereby promoting contact expansion — first, by providing adhesion tension that lowers interfacial tension at the cell-cell contact, and second, by signaling to the actomyosin cytoskeleton in order to reduce cortex tension and thus interfacial tension at the contact. The third function of cadherins in cell-cell contact formation is to stabilize the contact by resisting mechanical forces that pull on the contact.

Type IV collagen

What type of collagen is associated with the basement membrane?

Adherin Junctions

Zonula adherens (adhesion belt). Cadherins. initiate cell-cell contacts, and mediate the maturation and maintenance of the contact. Adherens junctions consist of the transmembrane protein E-cadherin, and intracellular components, p120-catenin, β-catenin and α-catenin. connects actin filament bundle in one cell with that in the next cell this type of cell junction is located right below tight junctions and provides a strong bond between the sides of adjacent epithelial cell membranes. While other junctions, like tight junctions, provide some support for and fusion of adjacent cells, their resistance to mechanical stress is relatively small compared to the much stronger adherens junctions. (PROVIDE GREATER RESISTANCE TO MECHANICAL STRESS)

alpha-actinin

a protein that bundles actin into parallel arrays and anchors actin to Z lines - found in the Z disc - binds to actin molecules of the thin filament and to titin

what are the 4 forms of anchoring junctions?

adherins junctions desmosomes hemidesmosomes actin-linked cell matrix adhesions (will speak of these when we speak about the basal lamina)

Hemidesmosomes

anchor cells to the basement membrane integrate with intermediate filaments wi in cell anchors to underlying tissue (basal lamina)

Integrins are required for

anchoring

dystonin

anchoring protein

plectin

anchoring proteins; links microtubules to intermediate filaments

Actin-linked cell-matrix adhesion junctions

anchors actin filaments in cell to ECM link cells to the extracellular matrix (ECM) and to each other and depend on interactions with the actin cytoskeleton. Both cell-ECM and cell-cell adhesion sites contain discrete, yet overlapping, functional modules. These modules establish physical associations with the actin cytoskeleton, locally modulate actin organization and dynamics, and trigger intracellular signaling pathways. Interplay between these modules generates distinct actin architectures that underlie different stages, types, and functions of cell-ECM and cell-cell adhesions. Actomyosin contractility is required to generate mature, stable adhesions, as well as to sense and translate the mechanical properties of the cellular environment into changes in cell organization and behavior.

Tight junctions structure

are composed of a claudin-based anastomosing network of TJ strands, at which plasma membranes of adjacent epithelial cells are closely attached to regulate the paracellular permeability. ... The paracellular permeability of ions and small tracers was increased in the dKO cells.

zonula adherens

between adjacent cells, weak glue, hold cells together. Simple epithelium.

stress fibers

bundles of actin filaments that help maintain skin cell shape and keep cells elongated

cadherins

calcium-dependent glycoproteins that hold similar cells together link adhesion belts form zipper-like structures between adjacent cells via homophilic binding to other cadherins in a calcium-dependent manner. Classic cadherins, such as the N-, P-, and E-cadherins, localize in adherence junctions to form an adhesion belt and build a connection with the actin-containing cytoskeleton. Cadherins are involved not only in cell-to-cell adhesion but also in morphogenesis and histogenesis. In the developing nervous system, cadherins are implicated in multiple functions in building neuronal structures. For example, N-cadherin plays roles in neurulation, the regionalization of neuroectoderm, neuronal migration, and axon growth and fasciculation. Recent studies indicate that cadherins are also involved in the development of sensory neurons, including visual and olfactory systems.

Cadherins

cell junction used when you want to resist separation of cell membrane to anchor cells together using microfilament (actin) and cadherin Adherens junctions are involved in a number of critical functions, including providing additional structural support. For example, they hold cardiac muscle cells tightly together as the heart expands and contracts. Adherens junctions are built primarily from cadherins, whose extracellular segments bind to each other and whose intracellular segments bind to catenins. Catenins are connected to actin filaments. transmembrane proteins that mediate cell-cell adhesion in animals. By regulating contact formation and stability, cadherins play a crucial role in tissue morphogenesis and homeostasis.

Connexins ------> connexons --------> ?

channels (gaps junctions)

what is tight junctions role in Na+ driven glucose symport?

confine transporters to appropriate and functional domains block backflow of glucose from basolateral side

Mechanical stress is transmitted from cell to cell by _____________ __________ anchored to what sites?

cytoskeletal filaments anchored to cell-matrix and cell-cell adhesion sites.

L-selectin

expressed on leukocytes

adhesion belts

extensive zones of adherens junctions that encircle a cell the way a belt encircles your waist form continuous bands around the perimeters of cells, connecting them together

anchoring junctions

fasten cells to one another or to EC material common in tissues subjected to friction & stretching outer layer of skin, muscle tissue of heart, neck of uterus, epithelial lining of GI tract Fasten cells to one another, common in stretched areas such as heart, uterus, and outer skin (adhesions) fasten cells together into sheets attachment of cytoskeleton of one cell to another cell or attachment of cytoskeleton of one cell to ECM enables groups of cells to fxn as unit actin or intermediate filaments bind to attachment proteins that are bound to transmembrane glycoproteins

anastamosing

fused networks of interwoven proteins The connection of separate parts of a branching system to form a network, as of leaf veins, blood vessels, or a river and its branches. 2. Medicine The surgical connection of separate or severed tubular hollow organs to form a continuous channel, as between two parts of the intestine.

Connexins make what type of cell junction?

gap junctions / Connexons

CAMs are important for...

growth of embryonic tissue and growth of nerve cells vital for cell-cell recognition/specificity adhesion interactions not as strong as adhesins implicated in autoimmunity disease and cancer

lectin domain

highly conserved domain of selectin that is able to interact with olgiosaccharides

connexons

hollow cylinders composed of proteins that span the entire width of the abutting membranes hold tissues/membranes together; hollow cylinders composed of proteins that span the entire width of the abutting membranes in gap junction, a protein linking adj cells channels formed by connexin proteins there can be several of these per gap junction, up to a few hundred

Occludins

integral proteins which fuse adjacent cells - form a nearly impermeable barrier

E-cadherin

intercellular adhesion; lose adhesion in malignant cells integral to embryogenesis

Cadherin-family adhesion proteins

intermediate (Keratin) anchoring proteins (catenins)

adheren junctions

joins an actin bundle in one cell to a similar bundle in a neighboring cell

VCAM

ligands firmly bind to activated B1-integrins on eosinophils, monocytes, and lymphocytes vascular cell adhesion molecule Leukocyte adhesion molecule defect

Extracellular matrix represented by the basal lamina (or basement membrane). Epithelial cell junctions consist of three types: what are they?

occluding (tight) junctions anchoring junctions channel forming junctions A fourth type, signal-relaying junctions, will be touched upon later.

Diapedesis Leukocyte Emigration

passage of blood cells (especially white blood cells) through intact capillary walls and into the surrounding tissue; leave vessels, crawl through endothelial cells that line the vessel; migrate to needed tissues WBC and platelets ICAMs will bind to integrins on WBC and ICAMs on endothelial cells

zonula occludens (Zo Proteins)

permeability barrier, e.g., stomach and urinary bladder, chemicals cannot pass between cells. support proteins on cytoplasmic side

P-selectin

platelets and endothelial cells

desmoplakin

protein in desmosome plaque that is relatively large and extended dimer that forms the junction between intermediate filaments and the TM adhesion proteins (desmoglein and desmocollin)

E-cadherin

responsible for cell-cell adhesion in normal tissues catenin major anchoring proteins; intracellular connection to actin cytoskeleton

CAMs (cell adhesion molecules)

sticky glycoproteins (cadherins and integrins) that are found on almost every cell. they act as desmosomes, arms that migrating cells use to haul themselves past one another, SOS signals sticking out from the blood vessel lining that rally protective white blood cells to a nearby infected or injured area, mechanical sensors that respond to changes in local tension or fluid movement by stimulating synthesis or degradation of tight junctions, transmitters of intracellular signals that direct cell migration, proliferation, and specialization transmembrane proteins that bind large areas of the plasma membrane to other cells or to extracellular materials massive super family of immunoglobulins; share antibody domains

Occluding Junctions

tight junctions; form a barrier that isolates the basolateral surfaces and deeper tissues from the contents of the lumen; multiprotein junctional complexes whose general function is to prevent leakage of transported solutes and water and seals the paracellular pathway. seals neighboring cells together in an epithelial sheath. prevents unwanted leakage of molecules between them also prevent proteins in apical membrane from diffusing too quickly down o the basolateral side and vice versa

transcellular transport

transport of materials through the cell; requires interaction with the cytoplasm and may require transport proteins

tight junctions

virtually (but also partly selectively) impermeable seals that encircle cells and bind them together into leakproof sheets. In other words, the plasma membranes of adjacent cells essentially fuse together tightly in order to limit the leakage of various substances between the two cells. What can and cannot go through all depends on the substance's size, charge, as well as the location and precise composition of the tight junctions in the part of the body in question. Tight junctions are located within our body's epithelia. Epithelia is the plural of epithelium. Epithelium is a word that refers to the covering of the body's internal and external surfaces. This includes organs (such as skin), blood vessels, and cavities. Thus, these tight junctions serve various functions, depending on what epithelium is in question. In the skin, they keep us somewhat watertight and help keep allergens out of our body. In the digestive system, they help prevent the leakage of digestive enzymes into our bloodstream. Tight junctions also serve as a structural support mechanism that help keep the epithelium together.