Module 10- Cell Junctions, Adhesion, and the ECM

An anchoring cell junction in which the cytoplasmic face of the plasma membrane is attached to actin filaments.

Adherens junction (zonula adherens)

The key organizational proteins found at tight junctions. There are 3 major members of this protein family, which are large scaffold proteins that provide the structural support onto which the tight junction is built.

Zonula occludins proteins (ZO)

A fibrous protein rich in glycine and proline that is a major component of the ECM in animals to confer tensile strength. This version of collagen is found in basal laminae.

Collagen type IV

A large, flexible fibrous ECM protein found in basal laminae, where it forms a sheetlike network. It is composed of 3 different polypeptide chains arranged into an asymmetrical cross that is held together by disulfide bonds.

Laminin

Proteins composed of gap junctions that are four-pass transmembrane proteins. Six of these proteins assemble in the plasma membrane to form a hemichannel.

Connexins

A large cytoskeletal adapter protein that is part of the complex that attaches the actin cytoskeleton indirectly to the short intracellular C terminal end of integrin proteins.

Talin

A glycoprotein linker protein that connects the laminin network to the type IV collagen network at basal laminae.

Nidogen

Long, linear, highly charged polysaccharides composed of repeating pairs of sugars, one of which is always an amino sugar. Mostly found covalently attached to a protein core in ECM proteoglycans.

Glycosaminoglycans (GAGs)

Anchoring cell junction, usually between 2 epithelial cells. Contain dense plaques of protein into which intermediate filaments in the 2 adjoining cells insert.

Desmosome (macula adherens)

The dependance of cell growth, proliferation, and survival on attachment to a substratum.

Anchorage dependance

A transmembrane protein found at tight junctions that is required to seal cell membranes together and prevent transepithelial leakage at the points where 3 adjacent epithelial cells meet.

Tricellulin

A proteoglycan linker protein that connects the laminin network to the type IV collagen network at basal laminae.

Perlecan

Cell-cell junction that seals adjacent epithelial cells together to prevent passage of most dissolved molecules from one side of the epithelial sheet to the other.

Tight junction (zonula occludins)

Communicating channel-forming cell-cell junction present in most animal tissues that allows ions and small molecules to pass from the cytoplasm of one cell to the cytoplasm of the next cell.

Gap junctions

Type of nonsulfated glycosaminoglycan with a regular repeating sequence of up to 25,000 identical disaccharide subunits and not linked to a core protein. Found in the fluid lubricating joints and other tissues.

Hyaluronan (hyaluronic acid)

Depends on intracellular regulatory signals that stimulate the ability of talin and other proteins to interact with the chain of integrin. Binding of talin to the chain triggers the unfolding of the external domains.

Inside-out activation (of integrins)

Proteins that bind groups of intracellular proteins into a complex, often anchoring the complex at a specific location in the cell.

Scaffold proteins

A cytoplasmic tyrosine kinase present at cell-matrix junctions (focal adhesions) in association with the cytoplasmic tail of integrins.

Focal adhesion kinase (FAK)

A half-circle shaped anchoring cell junction between the cytoskeleton of an epithelial cell and the basal lamina. These cytoskeletal intermediate filaments are indirectly linked via integrins to laminin molecules of the basal lamina.

Hemidesmosomes

Collagen molecules that do not form fibrils, but rather their ends associate to form a meshwork, such as type IV collagen in the basal lamina.

Network-forming collagens

A transmembrane adhesion protein involved in the attachment of cells to the ECM and to each other.

Integrins

A transmembrane protein found at tight junctions, but not essential for the assembly or structure of the tight junction. Rather, it is needed to limit junctional permeability.

Occludins

A proteoglycan found in cartilage that has approximately 100 attached glycosaminoglycans.

Aggrecan

A cell junction that attaches cells to neighboring cells or to the ECM.

Anchoring junction

Binding of an external ligand causes the extracellular domains to unfold and straighten. This causes the intracellular domains to move apart, exposing their binding site for talin.

Outside-in activation (of integrins)

The accumulation of many weak bonds together forms a strong cluster.

Velcro principle

Cell-surface transmembrane carbohydrate-binding proteins that mediate transient, Ca2+-dependent cell-cell adhesion in the bloodstream. Contain a conserved lectin domain.

Selectins

Water filled pores in the plasma membrane formed by a ring of 6 protein subunits. Half of a gap junction is formed by this structure on 2 adjoining cells forming a continuous channel through which ions and small molecules can pass.

Connexons

A protein with a flexible triple-stranded helical structure and binds to the surface of collagen fibrils. Mediates interaction of these collagen fibrils with one another and with other matrix macromolecules to help determine their organization in the matrix.

Fibril-associated collagen

Transmembrane adhesion proteins involved in homophilic Ca2+-dependent cell-cell attachment in animal tissues.

Cadherins

A large glycoprotein that binds to elastin and is essential for the integrity of elastic fibers. Mutations in this gene lead to Marfan Syndrome.

Fibrillin

A form of cellular transport that occurs across a cell.

Transcellular transport

Extensible fiber formed by proteins in many animal connective tissues that gives them their stretchability and resilience.

Elastic fibers

Cadherins act in this process to enable cells of similar types that express similar cadherins to recognize each other, stick to each other, and stay segregated from other cell types.

Cell sorting

Main endothelial cell proteins recognized by white blood cell integrins. Are members of the immunoglobulin superfamily and contain 1 or more Ig-like domains.

ICAMs (intercellular cell adhesion molecules)

A type of protease that has a reactive serine in the active site. This is one class of molecule used to degrade matrix proteins in the ECM.

Serine proteases

A highly regulated process that allows epithelial cells to lose their characteristic polarity and adhesiveness and take on a mesenchymal phenotype including enhanced migratory behavior.

Epithelial-mesenchymal transition (EMT)

A fibrous protein rich in glycine and proline that is a major component of the ECM in animals to confer tensile strength. This version of collagen is the most common and is found in skin, tendon, and bone.

Collagen type I

An adherens junction found in epithelia that forms a continuous zonula adherens just beneath the apical face of the epithelium. Each interacting cell is encircled in a sheet.

Adhesion belt

Extracellular proteins that form extensible fibers in connective tissues.

Elastins

Molecules that consist of one or more glycosaminoglycan chains attached to a core protein.

Proteoglycans

A form of cellular transport that occurs between adjacent cells.

Paracellular transport

A class of fibril-forming proteins that are common in skin and bone (type I) and have long rope-like structures with few to no interruptions. They assemble into fibrils.

Fibrillar collagen

Proteoglycans that are integral components of the plasma membrane.

Syndecans

The main transmembrane proteins that are essential for tight junction formation and function.

Claudins

Proteins with multiple binding sites for other matrix molecules (collagen; proteoglycans) or for receptors on cell surfaces (integrins). These proteins help to organize the matrix, attach cells to the ECM, guide cell movement during development, and bind and influence the function of growth factors and other small molecules produced by nearby cells.

Multi-domain glycoproteins

A fibrous protein rich in glycine and proline that is a major component of the ECM in animals to confer tensile strength. This version of collagen is found in cartilage.

Collagen type II

Extracellular matrix proteins involved in adhesion of cells to the matrix and guiding cell migration during embryogenesis. Integrins on the cell surface are receptors for these proteins.

Fibronectins

A thin mat of extracellular matrix that separates epithelial sheets, as well as other cell types (muscle or fat cells) from connective tissue.

Basal lamina (basement membrane)

A type of protease that requires a Ca2+ or Zn2+ cofactor and is present in the ECM where it degrades matrix proteins.

Matrix metalloproteases

Protein that binds tightly to a specific sugar due to a conserved carbohydrate-binding domain. Ex. selectins

Lectins

A network-forming collagen that when polymerized, forms anchoring fibrils, and is found beneath stratified squamous epithelia.

Collagen type VII