Subgroup II PAK-mediated phosphorylation regulates Ran activity during mitosis

Type Article
Date 2010-09
Language English
Author(s) Bompard Guillaume1, 2, 4, Rabeharivelo Gabriel1, 2, 4, Frank Marie1, 2, 4, Cau Julien1, 3, 4, Delsert Claude1, 2, 4, 5, Morin Nathalie1, 2, 4
Affiliation(s) 1 : Univ Montpellier 2, IFR 122, F-34293 Montpellier, France.
2 : CNRS, Ctr Rech Biochim Macromol, F-34293 Montpellier, France.
3 : CNRS, UPR 1142, Inst Human Genet, F-34396 Montpellier, France.
4 : Univ Montpellier 1, IFR 122, F-34293 Montpellier, France.
5 : IFREMER, Lab Genet & Pathol, F-17390 La Tremblade, France.
Source Journal Of Cell Biology (0021-9525) (Rockefeller Univ Press), 2010-09 , Vol. 190 , N. 5 , P. 807-822
DOI 10.1083/jcb.200912056
WOS© Times Cited 27
Abstract Ran is an essential GTPase that controls nucleocytoplasmic transport, mitosis, and nuclear envelope formation. These functions are regulated by interaction of Ran with different partners, and by formation of a Ran-GTP gradient emanating from chromatin. Here, we identify a novel level of Ran regulation. We show that Ran is a substrate for p21-activated kinase 4 (PAK4) and that its phosphorylation on serine-135 increases during mitosis. The endogenous phosphorylated Ran and active PAK4 dynamically associate with different components of the microtubule spindle during mitotic progression. A GDP-ound Ran phosphomimetic mutant cannot undergo RCC1-mediated GDP/GTP exchange and cannot induce microtubule asters in mitotic Xenopus egg extracts. Conversely, phosphorylation of GTP-bound Ran facilitates aster nucleation. Finally, phosphorylation of Ran on serine-135 impedes its binding to RCC1 and RanGAP1. Our study suggests that PAK4-mediated phosphorylation of GDP- or GTP-bound Ran regulates the assembly of Ran-dependent complexes on the mitotic spindle.
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