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Vol. 18, Issue 4, 1203-1219, April 2007

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Avl9p, a Member of a Novel Protein Superfamily, Functions in the Late Secretory Pathway

Edina Harsay^*,, and Randy Schekman

*Department of Molecular Biosciences, University of Kansas, Lawrence, KS 66045; and Department of Molecular and Cell Biology, Howard Hughes Medical Institute, University of California, Berkeley, CA 94720

Submitted November 22, 2006; Revised December 29, 2006; Accepted January 10, 2007
Monitoring Editor: Benjamin Glick

The branching of exocytic transport routes in both yeast and mammalian cells has complicated studies of the late secretory pathway, and the mechanisms involved in exocytic cargo sorting and exit from the Golgi and endosomes are not well understood. Because cargo can be sorted away from a blocked route and secreted by an alternate route, mutants defective in only one route do not exhibit a strong secretory phenotype and are therefore difficult to isolate. In a genetic screen designed to isolate such mutants, we identified a novel conserved protein, Avl9p, the absence of which conferred lethality in a vps1 apl2 strain background (lacking a dynamin and an adaptor-protein complex 1 subunit). Depletion of Avl9p in this strain resulted in secretory defects as well as accumulation of Golgi-like membranes. The triple mutant also had a depolarized actin cytoskeleton and defects in polarized secretion. Overexpression of Avl9p in wild-type cells resulted in vesicle accumulation and a post-Golgi defect in secretion. Phylogenetic analysis indicated evolutionary relationships between Avl9p and regulators of membrane traffic and actin function.

The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).

Address correspondence to: Edina Harsay (harsay{at}ku.edu)

Abbreviations used: AP, adaptor protein; AVL, AP-1 Vps1 LethalM; AH, Avl9 homology; ANR, Avl Nine Related; CSM, complete synthetic medium; DENN, differentially expressed in normal versus neoplastic; HMM, Hidden Markov Model; MEME/MAST, Multiple Em for Motif Elicitation/Motif Alignment and Search Tool; PtdIns, phosphatidylinositol; YPD, yeast extract, peptone, dextrose; 5-FOA, 5-fluoroorotic acid; 5-FAA, 5-fluoroanthranilic acid.