Cell Adhesion & Movement
Terms
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- cadherins
- Ca++-dependent CAMs; Transmembrane; EC1: cadherin-cadherin recognition; EC2: Ca++ binding; intracellular: bind to catenins, actin MFs; homotypic binding determined by amino acids next to HAV; often dimerize
- HAV
- Histidine, Alanine, Valine; recognized by cadherin EC1; on terminal tip of extracellular domain
- "Finding" a molecule
- Tag it: insert gene to express labeled protein; immunofluorescence
- "Losing" a molecule
- Molecular techniques: knock-out genes, etc; block with Fab
- "Moving" a molecule
- express it in a cell that doesn't normally express it; move it to another part
- ADAM
- a metalloprotease; CNC cells exocytose it; ADAM 13 can digest cadherin II; this allows CNC cells to migrate
- Ig-like CAMs
- tansmembrane; bound sugar molecules, can change stickiness; Ca++ insensitive; looks like Ab; outer parts can be modified by sialic acid
- Sialic Acid
- 10-C sugar; negatively charged; lowers adhesiveness; can be short or long; usually can bind to three sites on Ig-like CAMs
- collagen
- a class of glycoproteins; long, strong, triple-helical fibers; resists stretching; large part of ECM; contains lots of glycene & proline
- proteoglycans
- glycoproteins in which carb>>>protein; mucus component of ECM; complex structures; resist compression
- hyaluronic acid
- a glycosaminoglycan (GAG); part of proteoglycan
- GAGs
- HA, chondroitin sulfate, dermatan sulfate, keratan sulfate, hepanan sulfate
- fibronectin
- found in all (and only) animals looked at; large dimer; has multiple binding sites; binds cells to and organizes ECM; can bind to integrins
- integrin binding
- collagen - fibronectin - beta & gamma integrin - transmembrane region - talin - vinculin - alpha-actinin - actin MFs
- RGD tripeptide
- part of fibronectin needed for integrin binding
- cell crawling cycle
- protrusion, anchoring, cell body translocation, detachment
- membrane extension
- exocytosis of vesicles to increase membrane surface area; redistribution of surface (smoothing of folds)
- cytoskeleton protrusion
- transport proteins move monomeric actin from back of polymers to front; polymerization includes branching of MFs
- ARP2/3
- complex of 7 proteins that bind to MF & provide new site for polymerization; at Y junctions; binds to the side and caps barbed end of MF, adds new ATP-actin monomers
- Actin Binding Proteins
- crosslink MFs into parallel bundles (fascin) & meshwork (filamen); break down/depolymerize meshwork (cofilin, gelsolin); thymosin binds to actin monomers and buffers cell-substrate adhesion
- myosin
- binds to actin MFs, allows them to slide, can lead to expansion and contraction of meshwork; myosin II needed for good cell crawling, helps in development of cortical tension needed for contraction of cytoskeleton & detachment; myosin I possibly part of Arp2/3 complex
- focal adhesions
- patches of integrins, connected to bundles of actin with myosin for contracting (stress fibers); move in stationary cells, fixed in migrating cells
- Reynold's number
- inertial forces/viscous forces; is very low for cells
- inertial forces
- velocity, size, density of liquid
- 4 major techniques of experimental embryology
- 1. Defect; 2. Isolation; 3. Recombination; 4. Transplantation
- 6 cell processes in morphogenesis
- cell divisions (# & direction), shape changes, movement, growth, death, changes in membrane composition or secreted products
- differential adhesion hypothesis
- Model to explain patterns of cell sorting with thermodynamic principles-- cells interact to form aggregate with smallest interfacial free energy-- sorting & migration caused by changes in type & amount of adhesion