Cytoskeletal matrix

Neuromuscular transmission is initiated when an action potential travelling down the axon of a motor neurone arrives at the nerve terminal. Vesicles containing the neuromuscular transmitter, acetylcholine, are present in rows which line up either side of an "active zone". Active zones are transmitter release sites. The vesicles arrive at the active zones guided by the cytoskeletal matrix which is made up of microtubules, the contractile protein actin and the smooth endoplasmic reticulum. Attachment to the cytoskeleton is mediated by various proteins including s mapsin... 

Thus far, microtubules and actin filaments and their associated proteins have been discussed to advantage as independent cytoskeletal components. In actual fact, all of the components of the cytoskeleton (including intermediate filaments) are precisely integrated with one another (Langford, 1995), as well as with various cytoplasmic organelles, the nuclear membrane, the plasma membrane, and the extracellular matrix. In its totality the cytoskeleton subserves many coordinated and regulated functions in the cell ... 

Pratt BM, Harris AS, Morrow JS et al (1984) Mechanisms of cytoskeletal regulation. Modulation of aortic endothelial cell spectrin by the extracellular matrix. Am J Pathol 117 ... 

The transition from mesenchyme to epithelium involves biochemical changes in the cells and the extracellular matrix, N-CAM expression on cell surfaces disappears, replaced by L-CAM (uvomorulin). Vimentin, a characteristic cytoskeletal component of mesenchyme, disappears, and cytokeratin, characteristic of epithelia, appears. There is a decrease in collagen I extracellularly and an increase in the basement membrane components laminin and collagen IV. 

Receptors (adhesion receptors) that interact with macromolecular components of the extracellular matrix (such as collagen) and convey to the cytoskeletal system instructions on cell migration or adherence to the matrix. Integrins (discussed in Chapter 10) illustrate this general type of transduction mechanism. 

SH3 domains are used extensively by cytoskeletal and signaling proteins to mediate protein-protein interactions, and they do so through a proline-rich motif. This has a consensus sequence P-X-X-P. Another motif—the WW domain—also facilitates protein-protein interactions, and it too is based on proline. Its consensus sequence is P-P-X-Y (a Type I WW repeat as identified in the extracellular matrix receptor /3-dystroglycan) and this interacts with a WW domain in dystrophin or utrophin (Ilsley et al, 2002 Winder, 2001). These two motifs are interesting, not only because they are short and proline-rich, but because they are able to impose considerable specificity of interaction on the proteins involved. 

Buxboim A, Ivanovska IL, Discher D (2010) Matrix elasticity, cytoskeletal forces and physics of the nucleus how deeply do cells feel outside and in J Cell Sci 123 297-308... 

Integrins are a family of transmembrane heterodimeric glycoproteins that are receptors for specific epitopes of extracellular matrix proteins and for other cell-surface molecules (Kramer et al, 1993). Integrins exist as a dimer complex composed of an a-subunit (120-180 kD) noncovalently associated with a /1-subunit (90-110 kD) (Hynes, 1992). At least 8 /1-subunits and 14 -units have been identified and are concentrated at loci, called focal adhesion sites, of close proximity between cells and extracellular matrices on substrates (Hynes, 1992). Focal adhesion sites are points of aggregation of, and are physically associated with, intracellular cytoskeletal molecules that control, direct, and modulate cell function in response to extracellular signals (Schwartz, 1992). 

Adhesive interactions play critical roles in the migration of cells. These interactions are mediated by cell-surface receptors, the integrins that bind to components of the extra-celluar matrix and/or to ligands presented by adjacent cells. Consequently, these interactions lead to the formation of intracellular cytoskeletal assemblies and actin bundles (Fig. 4.4). 

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