Rac (GTPase)
Topic: Biology
From HandWiki - Reading time: 3 min
Rac is a subfamily of the Rho family of GTPases,[1] small (~21 kDa) signaling G proteins (more specifically a GTPase). Just as other G proteins, Rac acts as a molecular switch, remaining inactive while bound to GDP and activated once GEFs remove GDP, permitting GTP to bind. When bound to GTP, Rac is activated. In its activated state, Rac participates in the regulation of cell movement, through its involvement in structural changes to the actin Cytoskeleton.[2] By changing the cytoskeletal dynamics within the cell, Rac-GTPases are able to facilitate the recruitment of neutrophils to the infected tissues, and to regulate degranulation of azurophil and integrin-dependent phagocytosis.[3]
Activated Rac also regulates the effector functions of the target proteins involved in downstream signaling. As an essential subunit of NOX2 (NADPH oxidase enzyme complex), Rac is required for ROS (reactive oxygen species) production involved in the formation of NETs (neutrophil extracellular traps, thus, facilitating the pathogen and debris clearance by neutrophils, and the reduction of inflammation.[3]
The abnormal activities of Rac including its hyperactivation, resistance to degradation, and abnormal localization of its signaling protein components were found to facilitate the development of cancerous cells and resist to anticancer treatment.[4]
Recent experiments on Drosophila suggested that Rac could be involved in mediating the process of forgetting. Hyperactivation of Rac increases the memory decay whereas its inhibition prevents interference-induced forgetting and slows down a passive memory decay.[5][6]
Classification
The Rho family of GTPases includes Rac, Rho, and Cdc42 small G-protein groups. Rac comprises Rac1, Rac2, Rac3, and RhoG subgroups.
The extensive cross-talk within these groups of GTPase provides a significant impact on the biological responses of the cell, influencing the activity of the cell cycle machinery. Ras cooperates with Cdc42 to regulate Elk1 phosphorylation and transcriptional activity of SRF. Ras also cooperates with Rho and Ras to activate other downstream signaling pathways.[7]
References
- ↑ "Rho GTPases and actin dynamics in membrane protrusions and vesicle trafficking". Trends in Cell Biology 16 (10): 522–529. October 2006. doi:10.1016/j.tcb.2006.08.006. PMID 16949823.
- ↑ "Rac", Encyclopedia of Cancer, Springer Berlin Heidelberg, 2011, pp. 3133, doi:10.1007/978-3-642-16483-5_4891, ISBN 9783642164828
- ↑ 3.0 3.1 "Rac-GTPases and Rac-GEFs in neutrophil adhesion, migration and recruitment". European Journal of Clinical Investigation 48 Suppl 2 (Suppl Suppl 2): e12939. November 2018. doi:10.1111/eci.12939. PMID 29682742.
- ↑ "Rac signaling in tumorigenesis and as target for anticancer drug development". Drug Resistance Updates 9 (6): 274–287. December 2006. doi:10.1016/j.drup.2006.12.001. PMID 17234445.
- ↑ "Forgetting is regulated through Rac activity in Drosophila". Cell 140 (4): 579–589. February 2010. doi:10.1016/j.cell.2009.12.044. PMID 20178749.
- ↑ "Brain memory is actively cleared". http://scitechstory.com/2010/02/19/brain-memory-is-actively-cleared/.
- ↑ Bar-Sagi, Dafna; Hall, Alan (2010). "Ras and Rho GTPases" (in en). Cell 103 (2): 227–238. doi:10.1016/S0092-8674(00)00115-X. PMID 11057896.
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