Domain families cytoskeleton

Although the building blocks of the eukaryotic cytoskeleton appear to be ancient, the protein domains interacting with it appear to have emerged more recendy. Several actin-binding domain families, namely calponin homology, CH, actin depolymerisation factor (ADF), the Sla2p... 

The Ras GTP-mediated activation of P13-kinase links the Ras pathway with fimcti-ons of the Rho/Rac proteins. Members of this protein family within the Ras superfamily control formation of the cytoskeleton. The exact nature of the linkage with the Ras/PI3-kinase signal conduction to the Rac proteins is unknown. There is evidence that the product of the P13-kinase, Ptd-lns(3,4,5)P3, binds to the PH domain of the Vav protein and activates the latter. The Vav protein functions as a nucleotide exchange factor for the Rac GTPase (Han et al., 1998). The observation that activation of the Ras pathway is accompanied by reorganization of the cytoskeleton is in agreement with these findings. 

The contacts between two adjoining cell membranes are stabilized by specific cell adhesion molecules (CAMs), which include the Ca+2-dependent cadherins. These molecules appear to lead the way for cell-cell communications and are involved in mechanochemical transduction via cell-cell interactions. In some cell types, cadherins are concentrated within adherens junctions that are stretch-sensitive and their extracellular domains interact with cadherins on adjacent cells whereas their cytoplasmic domains provide attachment to the actin cytoskeleton via catenins and other cytoskeletal proteins. The Rho family is required for the establishment and maintenance of cadherin-based adherens junctions. The type of cadherin expressed in a cell can affect the specificity and the physiological properties of cell-cell interactions. 

The ability to bind actin is an intrinsic capacity of coronin proteins (reviewed in refs. 1, 2). In some family members, it is ofren hard to define the bona fide actin binding domain because most parts of the molecule possess actin binding properties. There is at least one family member, however, which until to date has not been shown to physically interact or colocalizc with actin. Although it is quite possible that future research will reveal specific conditions, processes or cell types where mammalian coronin 7 (CRN7 current official symbol C0R07) associates with actin cytoskeleton, the current data surest that this family member is unique in that its function is irrelevant to the regulation of the cytoskeleton. 

Pleckstrin homology (PH) domains comprise a large family of more than 200 domains and are found in many signal molecules such as Ser/Thr-specific protein kinases, tyrosine kinases, isoforms of phospholipase C (PL-CfS, y and <5), G nucleotide exchange factors, adaptor proteins, and proteins ofthe cytoskeleton (see also Fig. 8.11). Originally, the PH domain was discovered in the 47 kDa pleckstrin protein, which is the main substrate of protein kinase C in platelets. 

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