An IQGAP-related protein controls actin-ring formation and cytokinesis in yeast.

BACKGROUND: 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. RESULTS: 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. CONCLUSIONS: Yeast IQGAP-related protein, Iqg1, is an important regulator of cellular morphogenesis, inducing actin-ring formation in association with cytokinesis.

Cyk3, a novel SH3-domain protein, affects cytokinesis in yeast.

Cytokinesis requires the wholesale reorganization of the cytoskeleton and secretion to complete the division of one cell into two. In the budding yeast Saccharomyces cerevisiae, the IQGAP-related protein Iqg1 (Cyk1) promotes cytokinetic actin ring formation and is required for cytokinesis and viability [1-3]. As the actin ring is not essential for cytokinesis or viability, Iqg1 must act by another mechanism [4]. To uncover this mechanism, a screen for high-copy suppressors of the iqg1 lethal phenotype was performed. CYK3 suppressed the requirement for IQG1 in viability and cytokinesis without restoration of the actin ring, demonstrating that CYK3 promotes cytokinesis through an actomyosin-ring-independent pathway. CYK3 encodes a novel SH3-domain protein that was found in association with the actin ring and the mother-bud neck. cyk3 null cells had misshapen mother-bud necks and were deficient in cytokinesis. In the cyk3 null strain, actin rearrangements associated with cytokinesis appeared normal, suggesting that the phenotype reflects a defect in secretory targeting or septal synthesis. Deletion of either cyk3 or hof1 alone results in a mild cytokinetic phenotype [5-7], but deletion of both genes resulted in lethality and a complete cytokinetic block, suggesting overlapping function. Thus, Cyk3 appears to be important for cytokinesis and acts potentially downstream of Iqg1.