Differential effect of two stathmin/Op18 phosphorylation mutants on Xenopus embryo development

Citation
T. Kuntziger et al., Differential effect of two stathmin/Op18 phosphorylation mutants on Xenopus embryo development, J BIOL CHEM, 276(25), 2001, pp. 22979-22984
Citations number
43
Categorie Soggetti
Biochemistry & Biophysics
Journal title
JOURNAL OF BIOLOGICAL CHEMISTRY
ISSN journal
00219258 → ACNP
Volume
276
Issue
25
Year of publication
2001
Pages
22979 - 22984
Database
ISI
SICI code
0021-9258(20010622)276:25<22979:DEOTSP>2.0.ZU;2-O
Abstract
Stathmin/Op18 destabilizes microtubules in vitro and regulates microtubule polymerization in vivo. Both a microtubule catastrophe-promoting activity a nd a tubulin sequestering activity were demonstrated for stathlin in vitro, and both could contribute to microtubule depolymerization in vivo. Stathmi n activity can be turned down by extensive phosphorylation on its four phos phorylatable serines, and down-regulation of stathmin activity by phosphory lation is necessary for cells to proceed through mitosis. Tire show here th at microinjection of a nonphosphorylatable Ser to Ala (4A) quadruple mutant in Xenopus two-cell stage embryos results in cell cleavage arrest in the i njected blastomeres and aborted development, whereas injection of a pseudo- phosphorylated Ser to Glu quadruple mutant (4E) does not prevent normal dev elopment. Addition of these mutants to mitotic cytostatic factor-arrested e xtracts in which spindle assembly was induced led to a dramatic reduction o f spindle size with 4A stathmin, and to a moderate increase with 4E stathmi n, but both localized to spindle poles, interestingly the microtubule assem bly-dependent phosphorylation of endogenous stathmin was abolished in the p resence of 4A stathmin, but not of 4E stathmin. Altogether, this shows that the phosphorylation-mediated regulation of stathmin activity during the ce ll cycle is essential for early Xenopus embryonic development.