CELL JUNCTIONSDepartment of Natural Sciences University of St. La Salle Bacolod City
Cell junctions are theCELL JUNCTIONS structures where long term association between neighboring cells are established. The 3 most common kinds of cell junctions are tight junctions, adhesive/anchoring junctions, and gap/ communicating junctions. Adhesive junctions (desmosomes, hemidesmosomes and adherens junctions) link adjoining cells to each other and to the ECM. Although adhesive junction types are similar in structure and function, they contain distinct intracellular attachment proteins and transmembrane linker proteins.
The intracellular attachment proteins form a thick layer of fibrous material on the cytoplasmic side of the plasma membrane called a plaque which binds actin microfilaments in adherens junctions and intermediate filaments in desmosomes and hemidesmosomes. The transmembrane linker protein is anchored to the plaque by the cytoplasmic domain and binds the ECM or to the same proteins on other cells.
Distribution of celljunctions in 3 domainsof epithelial cells.
ZONULA OCCLUDENS extends around the entire perimeter of the cell, but typically located near the apex. Also known asterminal bars, tight or occluding junctions
Tight junctions consist of fused ridges of tightly packedtransmembrane junctional proteins. They regulate formation of the barriers by modulating cell proliferation, differentiation and polarization, and control barrier function by restricting paracellular diffusion. The above mechanisms may pave way for new therapeutic strategies in drug delivery across epithelial barriers.
Tight junctions block lateral movement of lipids and membrane proteins to keep a cell polarized. They leave no space between plasma membranes of adjacent cells to prevent the movement of molecules across cell layers. Sodium/glucose symport proteins and export by glucose transport proteins onthe basolateral surface and tight junctions prevent the lateral movement of these transport proteins.
ZONULA ADHERENS (intermediate junction, belt desmosomes) is basal to the zonula ocludens. The adjacent plasma membranes are separated by a gap of 15-20 nm, filled with an electron dense plaquecontaining a glycoprotein localized only in the membrane, (adherens junction-specific celladhesion molecule or A-CAM or E-cadherin).
Myosin, tropom yosin, α-actinin, andvinculin, actin- containingmicrofilaments insert into the plaque to stabilize the junction between epithelialcells, fibroblast s, smooth muscle cells and at intercalated discs.
MACULA ADHERENS or DESMOSOMES are bipartite structures of apposing cell membranes. An attachment plaque on the cytoplasmic side anchors tonofilaments which are intermediate filaments. Desmosomes form strongpoints of adhesion between cells in a tissue such that two adjoining cells are separated by a thin space of 25-35 nm, thedesmosome core, in which cadherin moleculesmediate cell-cell adhesion.
The plaques on the inner surfaces of cells joined by desmosomes have a mixture of intracellular attachment proteins (desmoplakins andplakoglobin) which interact with the tonofilament intermediate filaments.
Adherens junctions called FOCAL ADHESION can join a cell to the ECM, primarily through fibronectin receptors.
HEMIDESMOSOMES connect a cell, through a plaque, tothe basal lamina (ECM) by integrins. As in desmosomes,hemidesmosomes interact with tonofilament intermediatefilaments. Adherens junctions resemble desmosomes except two adjoining cells are separated by a thin space of 20-25 nm and connect to actin microfilaments in the cytoplasm. Some of the transmembrane glycoproteins are cadherins.
Hemidesmosomes occur at most basal surface of stratified squamous epithelia where the superficial layer lack junctional complexes, and the basal cells are exposed to the underlying CT. They serve mainly as sites ofattachment for the actin-based contractile system of the cytoplasm.
GAP JUNCTIONS (NEXUS)separate cells by 2-3 nm and allow direct electrical and chemical communication.
The nexus is a site where there is no actual fusion ofmembranes, and the gap is bridged by a connexon. These aretightly packed 7 nm wide hollow cylinders in two adjacent cell membranes that form a 3 nm thin hydrophilic channel that allows the passage of small molecules and ions.
The connexons of each membrane link to form continuous pores that bridge the intercellular gap, allowing passage of ions, cyclic AMP, amino acids and other small molecules. As sites of electronic coupling (reduced resistance to ion flow), it is the only type of junction mediating flow of current between cells important in intercellular communication and coordination. An influx of Ca+2 ions results in the closure of their channels, preventing spread of damage to other cells. Also found between osteocytes, astrocytes, cardiac muscle cells, smooth muscle cells, & endocrine cells. Cancer cells generally do not have gap junctions, so that cells fail to communicate their mitotic activity to each other, which may explain their uncontrolled growth.
When they were originally discovered cell junctions were considered to be relatively static structures. This was likely because they appeared to have a consistent, unchanging structure when viewed with the electron microscope. New techniques have revealed that proteins can move in and out of these junctions allowing the cell to sense the status of its intercellular adhesions. For example, occludin and ZO1, two proteins from adherens junctions have been shown to move into the nucleus to regulate gene activity. The interaction of junctional adhesion molecules with the cytoskeleton has also been shown to be a dynamic process that is still being elucidated.
(A) In a single cell, a subset of E-cadherin is found in a complex with Nectin-2α and components of the Exocyst complex. (B) Upon cell-cell adhesion, E- cadherin and Nectin-2α homodimers form trans-interactions with E-cadherinand Nectin-2α homodimers from the opposing cell, respectively. This interaction initiates the recruitment of microtubules, the Exocyst complex and the basal- lateral SNARE complex to the forming cell-cell contact. (C) Following cell-cell contact formation, microtubules extend into the contact, and post-Golgi carriers carrying basal-lateral cargo travel via microtubules to the forming contact. At the forming contact, the Exocyst and SNARE complexes are fully functional in mediating docking and fusion of basal-lateral post-Golgi carriers.