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Title

Spatial control of Cdc42 signalling by a GM130-RasGRF complex regulates polarity and tumorigenesis

AuthorsBaschieri, Francesco; Crespo, Piero ; Farhan, Hesso
Issue Date2014
PublisherNature Publishing Group
CitationNature Communications 5: 4839 (2014)
AbstractThe small GTPase Cdc42 is a key regulator of polarity, but little is known in mammals about its spatial regulation and the relevance of spatial Cdc42 pools for polarity. Here, we report the identification of a GM130-RasGRF complex as a regulator of Cdc42 at the Golgi. Silencing GM130 results in RasGRF-dependent inhibition of the Golgi pool of Cdc42, but does not affect Cdc42 at the cell surface. Furthermore, active Cdc42 at the Golgi is important to sustain asymmetric front-rear Cdc42-GTP distribution in directionally-migrating cells. Concurrently to Cdc42 inhibition, silencing GM130 also results in RasGRF-dependent Ras-ERK pathway activation. Moreover, depletion of GM130 is sufficient to induce E-cadherin down-regulation, indicative of a loss in cell polarity and epithelial identity. Accordingly, GM130 expression is frequently lost in colorectal and breast cancer patients. These findings establish a previously unrecognized role for the GM130-RasGRF-Cdc42 connection in regulating polarity and tumourigenesis.
DescriptionPMCID: PMC4449154.-- et al.
Publisher version (URL)http://dx.doi.org/10.1038/ncomms5839
URIhttp://hdl.handle.net/10261/130517
DOI10.1038/ncomms5839
Identifiersdoi: 10.1038/ncomms5839
e-issn: 2041-1723
Appears in Collections:(IBBTEC) Artículos
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