NUCLEAR EXPORT OF ACTIN - A NOVEL MECHANISM REGULATING THE SUBCELLULAR-LOCALIZATION OF A MAJOR CYTOSKELETAL PROTEIN

Citation
A. Wada et al., NUCLEAR EXPORT OF ACTIN - A NOVEL MECHANISM REGULATING THE SUBCELLULAR-LOCALIZATION OF A MAJOR CYTOSKELETAL PROTEIN, EMBO journal, 17(6), 1998, pp. 1635-1641
Citations number
28
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biology,"Cell Biology
Journal title
ISSN journal
0261-4189
Volume
17
Issue
6
Year of publication
1998
Pages
1635 - 1641
Database
ISI
SICI code
0261-4189(1998)17:6<1635:NEOA-A>2.0.ZU;2-1
Abstract
Actin is a highly conserved, ubiquitous cytoskeletal protein, which is essential for multiple cellular functions, Despite its small size (M- r = 42 000), unpolymerized forms of actin, as well as polymerized form s, exist primarily in the cytoplasm, excluded from the nucleus, Althou gh spatial control of actin is crucially important, the molecular mech anisms ensuring the cytoplasmic localization of unpolymerized actin ha ve not been revealed so far, In this paper we report that actin contai ns two leucine-rich type nuclear export signal (NES) sequences in the middle part of the molecule, which are both shown to be functional, Mo nomeric actin, when injected into the nucleus, was rapidly exported in a manner which was sensitive to leptomycin B (LMB), a specific inhibi tor of NES-dependent nuclear export, LMB treatment of cells prevented nuclear exclusion of endogenous actin, inducing its nuclear accumulati on, Furthermore, actin mutants with disrupted NESs accumulated in the nucleus, Expression of these NES-disrupted actin mutants, but not of w ildtype actin, induced a decrease in the proliferative potential of th e cell, These results reveal a novel molecular mechanism controlling t he subcellular distribution of actin.