dictyNews
Electronic Edition
Volume 36, number 15
June 3, 2011
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Abstracts
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The LRRK2-related Roco kinase Roco2 is regulated by Rab1A and
controls the actin cytoskeleton
Sebastien Kicka, Zhouxin Shen, Sarah J. Annesley, Paul R. Fisher,
Susan Lee, Steven Briggs and Richard A. Firtel
Mol. Biol Cell, in press
We identify a new pathway that is required for proper pseudopod formation.
We show that Roco2, an LRRK2-related Roco kinase, is activated in response
to chemoattractant stimulation and helps mediate cell polarization and
chemotaxis by regulating cortical F-actin polymerization and pseudopod
extension in a pathway that requires Rab1A. We found that Roco2 binds
the small GTPase Rab1A as well as the F-actin crosslinking protein filamin
(actin-binding protein 120, abp120) in vivo. We show that active Rab1A
(Rab1A-GTP) is required for and regulates Roco2 kinase activity in vivo,
and that filamin lies downstream from Roco2 to control pseudopod extension
during chemotaxis and random cell motility. Therefore, our study uncovered
a new signaling pathway that involves Rab1A and controls the actin
cytoskeleton and pseudopod extension, and thereby, cell polarity and motility.
These findings may have also implications in the regulation of other Roco
kinases, including possibly LRRK2, in metazoans.
Submitted by Rick Firtel [[log in to unmask]]
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