IQGAP1 is associated with nuclear envelope reformation and completion of abscission.
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.
a Children's Medical Research Institute; The University of Sydney ; Westmead , New South Wales , Australia.
Audrey T Y
AT
Lian
Peter G
PG
Hains
Boris
B
Sarcevic
Phillip J
PJ
Robinson
Megan
M
Chircop
D048749:Cytokinesis / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D009685:Nuclear Envelope / Q000235:genetics / Q000378:metabolism*; D020703:ras GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism*
C101203:IQ motif containing GTPase activating protein 1; D020703:ras GTPase-Activating Proteins
IQGAP1; abscission; cytokinesis; nuclear envelope; nuclear pore complex