Cell Adhesion Lecture (BIOL2020)

Cell adhesion Lecture 17 BIOL2020 Nicanor Arnold Hayer Cells in culture https://hayerlab.org/ In epithelial tissues, such as the lining of the gut or the epidermal covering of the skin, cells are tightly bound together into sheets called epithelia. Epithelial cells establish an apical-basal po...

Cell adhesion Lecture 17 BIOL2020 Nicanor Arnold Hayer Cells in culture https://hayerlab.org/ In epithelial tissues, such as the lining of the gut or the epidermal covering of the skin, cells are tightly bound together into sheets called epithelia. Epithelial cells establish an apical-basal polarity, which results from the differential distribution of phospholipids, protein complexes, and cytoskeletal components. ● Junctions connect cells at the lateral region Within the epithelium, cells are attached to each other directly by cell–cell junctions, where cytoskeletal filaments are anchored, transmitting stresses across the interiors of the cells Different types of junctions These three types of junctions are VERY important Adherens junctions associate with the actin cytoskeleton https://cshperspectives.cshlp.org/content/1/6/a002899.long The Cadherin/Catenin complex is the main component of the adherent junctions Many cadherins E-cadherin = epithelial N-Cadherin = neuronal ● ● Catenins link cadherins to the actin cytoskeleton Cadherins are homophilic (bind to each other) Cadherin is a transmembrane protein, Catenin is cytoplasmic Ca2+ ● Cadherin-Cadherin binding is Ca2+ dependant beta-catenin Cadherin Cell membrane The cadherin superfamily members all have extracellular portions containing multiple copies of the extracellular cadherin domain. Each cadherin domain forms a more-or-less rigid unit, joined to the next cadherin domain by a hinge. Ca2+ ions bind to each hinge and prevent it from flexing. When Ca2+ is removed, the hinges flex, and the structure becomes floppy cadherins = Calcium Adherins Typical Cadherins are Homophilic not Heterophilic. Atypical Cadherins are heterophilic. Cadherins mediate highly selective recognition, enabling cells of a similar type to stick together and to stay segregated from other types of cells. ● Cells are sorted by the type of cadherin and amounts of cadherins Assembly of Strong Cell–Cell Adhesions Requires Changes in the Actin Cytoskeleton Cadherins generate local signals to inhibit the GTPase Rho and activate the GTPase Rac Catenins Link Classical Cadherins to the Actin Cytoskeleton Heterophilic cadherins are called atypical Fat and Dachsous are atypical cadherins Ft and Ds are heterophilic because their role in planar cell polarity The collective alignment of cell polarity across the tissue plane is a phenomenon known as planar cell polarity Keep the seal: tight junctions epithelia are selective permeability barriers, This barrier function requires that the adjacent cells be sealed together by tight junctions, so that molecules cannot leak freely across the cell sheet. tight junctions are visualized by freeze-fracture electron microscopy, they are seen as a branching network of sealing strands that completely encircles the apical end of each cell The main transmembrane proteins forming these strands are the claudins the related proteins occludins Claudins form selective channels allowing specific ions to cross the tight-junctional barrier, from one extracellular space to another. Lateral view Top view https://pubs.acs.org/doi/10.1021/acs.jpcb.8b06484 Tight junctions in insects are called Septate junctions, they are organized differently, but have the same function Septate junctions are also made out of claudins Two experiments that evidence of permeability barrier Normal fly Mutant fly without septate junctions Without septate junctions, blue dye in the food diffuses through the gut epithelium dye diffusion in blocked by the junction Gap junctions Gap junctions are clusters of channels that join two cells together and consist of building blocks of two connexons or hemichannels, one contributed by each of the communicating cells. https://biosignaling.biomedcentral.com/articles/10.1186/1478-811X-7-4 Each connexon or hemichannel is formed of a complex of six connexin proteins. Vertebrate gap junctions are formed by connexins, while invertebrate gap junctions are formed by innexins. Vertebrates Vertebrates Invertebrates Gap junctions have a pore size of about 1.4 nm, which allows the exchange of inorganic ions and small molecules, but not of macromolecules Both connexin and innexin form similar sized pores Connexin https://www.nature.com/articles/nature07869 Innexin https://www.nature.com/articles/ncomms13681 summary Tight junctions ● semi impermeable ● claudins ● insect equivalent septate junction Adherens junctions ● strong cell-cell adhesion ● bound to actin cytoskeleton ● cadherin/catenin Gap junctions ● connect cytoplasms ● connexins/innexins