Genome-wide lethality screen identifies new PI4,5P2 effectors that regulate the actin cytoskeleton

Audhya, Anjon and Loewith, Robbie and Parsons, Ainslie B. and Gao, Lu and Tabuchi, Mitsuaki and Zhou, Huilin and Boone, Charles and Hall, Michael N. and Emr, Scott D.. (2004) Genome-wide lethality screen identifies new PI4,5P2 effectors that regulate the actin cytoskeleton. The EMBO Journal, 23 (19). pp. 3747-3757.

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Official URL: http://edoc.unibas.ch/dok/A5262071

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To further understand the roles played by the essential phosphoinositide PI4,5P(2), we have used a synthetic lethal analysis, which systematically combined the mss4(ts) mutation, partially defective in PI4P 5-kinase activity, with each of approximately 4700 deletion mutations. This genomic screening technique uncovered numerous new candidate effectors and regulators of PI4,5P(2) in yeast. In particular, we identified Slm1 (Yil105c), a previously uncharacterized PI4,5P(2) binding protein. Like Mss4, Slm1 and its homolog Slm2 (Ynl047c) were required for actin cytoskeleton polarization and viability. Co-immunoprecipitation experiments revealed that Slm1 interacts with a component of TORC2, a Tor2 kinase-containing complex, which also regulates the actin cytoskeleton. Consistent with these findings, phosphorylation of Slm1 and Slm2 was dependent on TORC2 protein kinase activity, both in vivo and in vitro, and Slm1 localization required both PI4,5P(2) and functional TORC2. Together, these data suggest that Slm1 and Slm2 function downstream of PI4,5P(2) and the TORC2 kinase pathway to control actin cytoskeleton organization.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Growth & Development > Biochemistry (Hall)
UniBasel Contributors:Hall, Michael N.
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Nature Publishing Group
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:09 Nov 2017 08:34
Deposited On:22 Mar 2012 13:23

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