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J. Biol. Chem., Vol. 279, Issue 35, 36962-36971, August 27, 2004

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Involvement of the Late Secretory Pathway in Actin Regulation and mRNA Transport in Yeast^*

Stella Aronov and Jeffrey E. Gerst

From the Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel

Both the delivery of secretory vesicles and asymmetric distribution of mRNA to the bud are dependent upon the actin cytoskeleton in yeast. Here we examined whether components of the exocytic apparatus play a role in mRNA transport. By screening secretion mutants in situ and in vivo, we found that all had an altered pattern of ASH1 mRNA localization. These included alleles of CDC42 and RHO3 (cdc42-6 and rho3-V51) thought to regulate specifically the fusion of secretory vesicles but were found to affect strongly the cytoskeleton as well. Most interestingly, mutations in late secretion-related genes not directly involved in actin regulation also showed substantial alterations in ASH1 mRNA distribution. These included mutations in genes encoding components of the exocyst (SEC10 and SEC15), SNARE regulatory proteins (SEC1, SEC4, and SRO7), SNAREs (SEC9 and SSO1/2), and proteins involved in Golgi export (PIK1 and YPT31/32). Importantly, prominent defects in the actin cytoskeleton were observed in all of these strains, thus implicating a known causal relationship between the deregulation of actin and the inhibition of mRNA transport. Our novel observations suggest that vesicular transport regulates the actin cytoskeleton in yeast (and not just vice versa) leading to subsequent defects in mRNA transport and localization.

Received for publication, February 25, 2004 , and in revised form, June 8, 2004.

^* This work was supported in part by a grant from the Minerva Foundation, Germany (to J. E. G.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Supported by the Forchheimer Center for Molecular Genetics and by an Ann Abrams Stone post-doctoral fellowship from the Feinberg Graduate School.

Holds the Henry Kaplan Chair in Cancer Research. To whom correspondence should be addressed. Tel.: 972-8-9342106; Fax: 972-8-9344108; E-mail: jeffrey.gerst{at}weizmann.ac.il.

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