IQGAP1 is associated with nuclear envelope reformation and completion of abscission

Abstract

The final stage of mitosis is cytokinesis, which results in 2 independent daughter cells. Cytokinesis has 2 phases: membrane ingression followed by membrane abscission. IQGAP1 is a scaffold protein that interacts with proteins implicated in mitosis, including F-actin, myosin and CaM. IQGAP1 in yeast recruits actin and myosin II filaments to the contractile ring for membrane ingression. In contrast, we show that mammalian IQGAP1 is not required for ingression, but coordinates nuclear pore complex (NPC) reassembly and completion of abscission. Depletion of IQGAP1 disrupts Nup98 and mAb414 nuclear envelope localization and delays abscission timing. IQGAP1 phosphorylation increases 15-fold upon mitotic entry at S86, S330 and T1434, with the latter site being targeted by CDK2/Cyclin A and CDK1/Cyclin A/ B in vitro. Expressing the phospho-deficient mutant IQGAP1-S330A impairs NPC reassembly in cells undergoing abscission. Thus, mammalian IQGAP1 functions later in mitosis than its yeast counterpart to regulate nuclear pore assembly in a S330 phosphorylation-dependent manner during the abscission phase of cytokinesis.

MicroRNA‐122 regulates polyploidization in the murine liver

“…Finally, we searched the literature for genes involved in cytokinesis that were also validated miR‐122 targets. We identified Cux1 , Iqgap1 , Mapre1 , and Rhoa , genes that have been implicated in cytokinesis and that have been demonstrated to be up‐regulated in Mir122 ‐deficient livers (Table ). Three of the targets, Rhoa , Mapre1 , and Nedd4l , were identified by multiple methods, which supports our screening approach.…”

“…Similar to previous results, we found that Mapre1 was up‐regulated 3‐fold to 5‐fold in Mir122 ‐KO livers (Fig. B,C). Iqgap1 is a Ras guanosine triphosphatase‐activating‐like protein that localizes to the spindle midbody during cytokinesis, where it promotes abscission and completion of cytokinesis . Depletion of Iqgap1 leads to a dramatic increase in the number of binucleate and multinucleate cells .…”

Arv1 promotes cell division by recruiting IQGAP1 and myosin to the cleavage furrow

“…Moreover we found IQGAP1 to facilitate cell division and to localize to the cleavage furrow in accordance to previous studies. 36,37 Interestingly, this localization of IQGAP1 was observed to be Arv1-dependent, but not vice versa, suggesting that IQGAP1 functions downstream of Arv1. Based on our immunoprecipiation analysis indicating that IQGAP1 associates with Arv1 much more efficiently than MYH9 and MYL9, and previous studies in yeast indicating that IQGAP promotes 6).…”

“…Consistently, IQGAP1 was recently shown to stimulate nuclear pore reformation. 37 Interestingly, that manipulation of plasma membrane-cholesterol and Arv1 depletions affected the recruitment of IQGAP1, MYH9 and MYL differently indicates a scaffolding role of Arv1 during the assembly of the actomyosin ring independently of its cholesterol-transporting capacity. The compromised intracellular transport due to the U18666A-treatment yielded an accumulation of Arv1 protein, which further indicates that lipids modulate its expression (data not shown, will be addressed further).…”

HIV corruption of the Arp2/3-Cdc42-IQGAP1 axis to hijack cortical F-Actin to promote cell-cell viral spread

“…Cdc42 activity is initially important for maturation of the contractile actin ring, but inactivation of this Rho-GTPase is then required to allow F-actin clearance from the midbody and the final step of daughter cell abscission [113][114][115]. The interaction between IQGAP1 and Cdc42 likely plays a pivotal role in regulating cytokinesis [116,117], whereas the interaction between IQGAP1 and ESCRT proteins such as TSG101 may be required to complete abscission [101,118]. Thus, IQGAP1 may serve as a scaffolding center that enables coordination and cross-signaling of F-actin remodelling and abscission events during both cytokinesis and the VS. A hypothetical model for the role of IQGAP1 at the VS is provided in Figure 9.…”