Cytoskeleton remodeling Regulation of actin cytoskeleton by Rho GTPases

Regulation of actin cytoskeleton by Rho GTPases

Ras homolog gene family, member A ( RhoA ) downstream effector Rho-associated,coiled-coil containing protein kinase ( ROCK ) directly phosphorylates LIM domainkinases 1 and 2 ( LIMK1 and LIMK2 ) that in turn phosphorylatesCofilin. Cofilin exhibits Actin -depolymerizing activity followedby reorganization of the Actin cytoskeleton [1].

The activated ROCK also subsequently phosphorylates and inactivates the Myosinlight chain phosphatase ( MLCP ) [2] that attenuates Myosin lightchains ( MELC ) (myosin light chains) and Myosin light chain regulatory (MRLC ) phosphorylation [3].

Ras-related C3 botulinum toxin substrate 1 ( Rac1 ) downstream effector P21protein-activated kinase 1 ( PAK1 ) directly phosphorylates LIMK1 [4], inhibits MLCK [5], activates MRLC [6]and ARP2 actin-related protein 2 and 3 ( Arp2/3 ) complex [7].Arp2/3 complex nucleates new Actin filaments from the sides of preexistingfilaments. [8]. Also, WAS protein family member 1 ( WAVE ) plays acritical role downstream of Rac in that it regulates the Actin cytoskeletonrequired for membrane ruffling. WAVE share function as an inducer of Actinreorganization through profiling [9].

Cell division cycle 42 ( CDC42 ) initiates Wiskott-Aldrich syndrome (WASP )/ Arp2/3 nucleation of Actin [10]. Recruitment offactors, including Profilin, by WASP stimulates cellular Actin-based motility [11].

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