Stathmin/Op18 phosphorylation is regulated by microtubule assembly.
Stathmin/Op 18 is a microtubule (MT) dynamics-regulating protein that has been shown to have both catastrophe-promoting and tubulin-sequestering activities. The level of stathmin/Op18 phosphorylation was proved both in vitro and in vivo to be important in modulating its MT-destabilizing activity. To understand the in vivo regulation of stathmin/Op18 activity, we investigated whether MT assembly itself could control phosphorylation of stathmin/Op18 and thus its MT-destabilizing activity. We found that MT nucleation by centrosomes from Xenopus sperm or somatic cells and MT assembly promoted by dimethyl sulfoxide or paclitaxel induced stathmin/Op18 hyperphosphorylation in Xenopus egg extracts, leading to new stathmin/Op18 isoforms phosphorylated on Ser 16. The MT-dependent phosphorylation of stathmin/Op18 took place in interphase extracts as well, and was also observed in somatic cells. We show that the MT-dependent phosphorylation of stathmin/Op18 on Ser 16 is mediated by an activity associated to the MTs, and that it is responsible for the stathmin/Op18 hyperphosphorylation reported to be induced by the addition of "mitotic chromatin." Our results suggest the existence of a positive feedback loop, which could represent a novel mechanism contributing to MT network control.
Küntziger
T
T
Institut Curie, Section Recherche, Unité Mixte de Recherche 144 Centre National de la Recherche Scientifique, 75248 Paris Cedex 05, France.
Gavet
O
O
Manceau
V
V
Sobel
A
A
Bornens
M
M
D000818:Animals; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D018385:Centrosome / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006367:HeLa Cells; D006801:Humans; D007399:Interphase / Q000502:physiology; D008297:Male; D008868:Microtubule Proteins; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism*; D015739:Nocodazole / Q000494:pharmacology; D010063:Ovum / Q000378:metabolism / Q000648:ultrastructure; D017239:Paclitaxel / Q000494:pharmacology; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D020033:Protein Isoforms; D012694:Serine / Q000378:metabolism; D013094:Spermatozoa / Q000378:metabolism / Q000648:ultrastructure; D050777:Stathmin; D014981:Xenopus; D029867:Xenopus Proteins
D004791:Enzyme Inhibitors; D008868:Microtubule Proteins; D010750:Phosphoproteins; D020033:Protein Isoforms; C493996:STMN1 protein, Xenopus; C493995:STMN1 protein, human; D050777:Stathmin; D029867:Xenopus Proteins; D012694:Serine; D017239:Paclitaxel; D015739:Nocodazole