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

Edina Harsay* ${dagger}$ and Randy Schekman ${dagger}$

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

Monitoring Editor: Benjamin Glick

The branching of exocytictransport routes in both yeast and mammalian cells has complicatedstudies of the late secretory pathway, and the mechanisms involvedin exocytic cargo sorting and exit from the Golgi and endosomesare not well understood. Because cargo can be sorted away froma blocked route and secreted by an alternate route, mutantsdefective in only one route do not exhibit a strong secretoryphenotype and are therefore difficult to isolate. In a geneticscreen designed to isolate such mutants, we identified a novelconserved protein, Avl9p, the absence of which conferred lethalityin a vps1 ${Delta}$ apl2 ${Delta}$ strain background (lacking a dynamin and an adaptor-proteincomplex 1 subunit). Depletion of Avl9p in this strain resultedin secretory defects as well as accumulation of Golgi-like membranes.The triple mutant also had a depolarized actin cytoskeletonand defects in polarized secretion. Overexpression of Avl9pin wild type cells resulted in vesicle accumulation and a post-Golgidefect in secretion. Phylogenetic analysis indicated evolutionaryrelationships between Avl9p and regulators of membrane trafficand actin function.

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