Epp J A, Chant J
Department of Molecular and Cellular Biology Harvard University 7 Divinity Avenue, Cambridge, Massachusetts 02138, USA.
Curr Biol. 1997 Dec 1;7(12):921-9. doi: 10.1016/s0960-9822(06)00411-8.
Proteins of the IQGAP family have been identified as candidate effectors for the Rho family of GTPases; however, little is known about their cellular functions. The domain structures of IQGAP family members make them excellent candidates as regulators of the cytoskeleton: their sequences include an actin-binding domain homologous to that found in calponin, IQ motifs for interaction with calmodulin, and a GTPase-binding domain.
The genomic sequence of Saccharomyces cerevisiae revealed a single gene encoding an IQGAP family member (denoted IQGAP-related protein: Iqg1). Iqg1 and IQGAPs share similarity along their entire length, with an amino-terminal calponin-homology (CH) domain, IQ repeats, and a conserved carboxyl terminus. In contrast to IQGAPs, Iqg1 lacks an identifiable GAP motif, a WW domain, and IR repeats, although the functions of these domains in IQGAPs are not well defined. Deletion of the IQG1 gene resulted in lethality. Cellular defects included a deficiency in cytokinesis, altered actin organization, aberrant nuclear segregation, and cell lysis. The primary defect appeared to be a cytokinesis defect, and the other problems possibly arose as a consequence of this initial defect. Consistent with a role in cytokinesis, Iqg1 co-localizes with an actin ring encircling the mother-bud neck late in the cell cycle -a putative cytokinetic ring. IQG1 overexpression resulted in premature actin-ring formation, suggesting that Iqg1 activity temporally controls formation of this structure during the cell cycle.
Yeast IQGAP-related protein, Iqg1, is an important regulator of cellular morphogenesis, inducing actin-ring formation in association with cytokinesis.
IQGAP家族蛋白已被确定为Rho家族GTP酶的候选效应器；然而，人们对其细胞功能知之甚少。IQGAP家族成员的结构域结构使其成为细胞骨架调节因子的优秀候选者：它们的序列包括一个与钙调蛋白中发现的肌动蛋白结合结构域同源的结构域、与钙调蛋白相互作用的IQ基序以及一个GTP酶结合结构域。
酿酒酵母的基因组序列显示有一个单一基因编码IQGAP家族成员（称为IQGAP相关蛋白：Iqg1）。Iqg1与IQGAPs在全长上具有相似性，具有一个氨基末端钙调蛋白同源（CH）结构域、IQ重复序列和一个保守的羧基末端。与IQGAPs不同，Iqg1缺乏可识别的GAP基序、WW结构域和IR重复序列，尽管这些结构域在IQGAPs中的功能尚未明确界定。IQG1基因的缺失导致致死性。细胞缺陷包括胞质分裂缺陷、肌动蛋白组织改变、核分离异常和细胞裂解。主要缺陷似乎是胞质分裂缺陷，其他问题可能是由这个初始缺陷导致的。与在胞质分裂中的作用一致，Iqg1在细胞周期后期与环绕母芽颈部的肌动蛋白环共定位——一个假定的胞质分裂环。IQG1的过表达导致肌动蛋白环过早形成，表明Iqg1的活性在细胞周期中暂时控制这个结构的形成。
酵母IQGAP相关蛋白Iqg1是细胞形态发生的重要调节因子，在胞质分裂过程中诱导肌动蛋白环的形成。
