Genome-wide lethality screen identifies new PI4,5P2 effectors that regulate the actin cytoskeleton
AUTOR(ES)
Audhya, Anjon
FONTE
Nature Publishing Group
RESUMO
To further understand the roles played by the essential phosphoinositide PI4,5P2, we have used a synthetic lethal analysis, which systematically combined the mss4ts 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 PI4,5P2 in yeast. In particular, we identified Slm1 (Yil105c), a previously uncharacterized PI4,5P2 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 PI4,5P2 and functional TORC2. Together, these data suggest that Slm1 and Slm2 function downstream of PI4,5P2 and the TORC2 kinase pathway to control actin cytoskeleton organization.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=522789Documentos Relacionados
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