Format

Send to

Choose Destination
Nat Cell Biol. 2009 Oct;11(10):1191-6. doi: 10.1038/ncb1961. Epub 2009 Sep 20.

MyosinV controls PTEN function and neuronal cell size.

Author information

1
MRC Centre for Developmental Neurobiology, New Hunt's House, King's College London, London SE1 1UL, UK.

Erratum in

  • Nat Cell Biol. 2009 Nov;11(11):1387.

Abstract

The tumour suppressor PTEN can inhibit cell proliferation and migration as well as control cell growth, in different cell types. PTEN functions predominately as a lipid phosphatase, converting PtdIns(3,4,5)P(3) to PtdIns(4,5)P(2), thereby antagonizing PI(3)K (phosphoinositide 3-kinase) and its established downstream effector pathways. However, much is unclear concerning the mechanisms that regulate PTEN movement to the cell membrane, which is necessary for its activity towards PtdIns(3,4,5)P(3) (Refs 3, 4, 5). Here we show a requirement for functional motor proteins in the control of PI3K signalling, involving a previously unknown association between PTEN and myosinV. FRET (Förster resonance energy transfer) measurements revealed that PTEN interacts directly with myosinV, which is dependent on PTEN phosphorylation mediated by CK2 and/or GSK3. Inactivation of myosinV-transport function in neurons increased cell size, which, in line with known attributes of PTEN-loss, required PI(3)K and mTor. Our data demonstrate a myosin-based transport mechanism that regulates PTEN function, providing new insights into the signalling networks regulating cell growth.

Comment in

PMID:
19767745
PMCID:
PMC2756284
DOI:
10.1038/ncb1961
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center