Rac GTPase-activating protein 1

Definition:

Component of the centralspindlin complex that serves as a microtubule-dependent and Rho-mediated signaling required for the myosin contractile ring formation during the cell cycle cytokinesis. Required for proper attachment of the midbody to the cell membrane during cytokinesis. Plays key roles in controlling cell growth and differentiation of hematopoietic cells through mechanisms other than regulating Rac GTPase activity. Has a critical role in erythropoiesis. Also involved in the regulation of growth-related processes in adipocytes and myoblasts. May be involved in regulating spermatogenesis and in the RACGAP1 pathway in neuronal proliferation. Shows strong GAP (GTPase activation) activity towards CDC42 and RAC1 and less towards RHOA. Essential for the early stages of embryogenesis. May play a role in regulating cortical activity through RHOA during cytokinesis. May participate in the regulation of sulfate transport in male germ cells.

References:

[1]. Jae-Seon Lee, et al. MgcRacGAP regulates cortical activity through RhoA during cytokinesis. Exp Cell Res. 2004 Feb 15;293(2):275-82. [Content Brief]

[2]. Keiju Kamijo, et al. Dissecting the role of Rho-mediated signaling in contractile ring formation. Mol Biol Cell. 2006 Jan;17(1):43-55. [Content Brief]

[3]. Ozlem Yüce, et al. An ECT2-centralspindlin complex regulates the localization and function of RhoA. J Cell Biol. 2005 Aug 15;170(4):571-82. [Content Brief]

[4]. T Kawashima, et al. MgcRacGAP is involved in the control of growth and differentiation of hematopoietic cells. Blood. 2000 Sep 15;96(6):2116-24. [Content Brief]

[5]. Fabian Oceguera-Yanez, et al. Ect2 and MgcRacGAP regulate the activation and function of Cdc42 in mitosis. J Cell Biol. 2005 Jan 17;168(2):221-32. [Content Brief]

[6]. Sergey Lekomtsev, et al. Centralspindlin links the mitotic spindle to the plasma membrane during cytokinesis. Nature. 2012 Dec 13;492(7428):276-9. [Content Brief]

[7]. K Hirose, et al. MgcRacGAP is involved in cytokinesis through associating with mitotic spindle and midbody. J Biol Chem. 2001 Feb 23;276(8):5821-8. [Content Brief]

[8]. Wei-meng Zhao, et al. MgcRacGAP controls the assembly of the contractile ring and the initiation of cytokinesis. Proc Natl Acad Sci U S A. 2005 Sep 13;102(37):13158-63. [Content Brief]

[9]. Benjamin A Wolfe, et al. Polo-like kinase 1 directs assembly of the HsCyk-4 RhoGAP/Ect2 RhoGEF complex to initiate cleavage furrow formation. PLoS Biol. 2009 May 5;7(5):e1000110. [Content Brief]

[10]. Masanori Mishima, et al. Central spindle assembly and cytokinesis require a kinesin-like protein/RhoGAP complex with microtubule bundling activity. Dev Cell. 2002 Jan;2(1):41-54. [Content Brief]

[11]. Sandeep N Wontakal, et al. RACGAP1 variants in a sporadic case of CDA III implicate the dysfunction of centralspindlin as the basis of the disease. Blood. 2022 Mar 3;139(9):1413-1418. [Content Brief]

[12]. A Toure, et al. Tat1, a novel sulfate transporter specifically expressed in human male germ cells and potentially linked to rhogtpase signaling. J Biol Chem. 2001 Jun 8;276(23):20309-15. [Content Brief]

[13]. Mark E Burkard, et al. Plk1 self-organization and priming phosphorylation of HsCYK-4 at the spindle midzone regulate the onset of division in human cells. PLoS Biol. 2009 May 5;7(5):e1000111. [Content Brief]

[14]. A Touré, et al. MgcRacGAP, a new human GTPase-activating protein for Rac and Cdc42 similar to Drosophila rotundRacGAP gene product, is expressed in male germ cells. J Biol Chem. 1998 Mar 13;273(11):6019-23. [Content Brief]

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