Why is cell adhesion important?
It allows for organization of multicellular structures such as
tissue and organs
Junctional
Cell-to-Cell
Non-junctional
Cell-to-ECM
Critical to cell communication and tissue formation
cell adhesion
ECM
Consists of macromolecules secreted by cells into extracellular space, it is produced modified and oreinted by cells within it
glycoproteins in ECM
organise matrix and cell into ordered structure
Collagen in ECM
major component of basal lamina, strong adhesion of cells to basal lamina
laminin
fibronectin
Cell-to-ECM attatchment
can provide signals for biological processes, and depending on cell-tissue, attachment behaviour and function can vary
integrins
cells ability to bind adhesive glycoproteins depends on expression of membrane receptors that can bind them.
fibronectin receptor complex
binds fibronectin, vitronectrin and laminin (arginine-glycine-aspartate (RGD)) on outside of cell, and actin cytoskeleton on inside of cell. It spans the cell membrane, binding fibronectin in ECM and anchorages cytoskeleton on inside
Integrin-matrix adhesion can regulate
cell signalling
gene expression
mitosis
apoptosis
cell differentiation
Focal adhesion
macromolecular structure >50 proteins
FA participate in:
anchorage, integrin-dependent signalling and actin dynamics
FA components
scaffolding molecules, GTPases and enzymes. Numerous proteins that can shuffle between focal adhesion and nuclear compartments allowing communication between subcellular domains
FA signalling
Tyrosine phosphorylation of FA proteins (paxillin and vinculin) by 2 kinases in FA (FAK & Src). Regulate dynamics and cell behaviour
Cell Migration
Cell moves by contracting the actin filaments against the fixed ECM because of dual binding
One of the most important contributors to cell fate in development
Cell Migration
Cell Migration Steps
FA assembly
complex intracellular intercations regulated by: Tyrosine phosphorylation, FAK, Rho
FA adhesion turnover/disassembly
regulated by: Kinase activity of Src and cleavage by calcium dependent protease, calpain
Intracellular force
Rho/ROCK increase FA and stress fibre formation
Extracellular force
rigidity of ECM strengthens integrin cytoskeletal link