A fab result

Abstract

Fab1p is essential for the activity of PtdIns(3)P 5-kinase and the maintenance of vacuolar size and membrane homeostasis. The importance of inositol phospholipids, especially those phosphorylated at the D3 position of the inositol ring, is hard to overstate. We are becoming increasingly familiar with their roles in signal transduction and membrane traffic. Lately, a new member of the family, PtdIns(3,5)P2, has been welcomed. Emr and colleagues suggest that the source of this lipid in Saccharomyces cerevisiae is the phosphorylation of PtdIns(3)P by Fab1p, a proposed PtdIns(3)P 5-kinase 1 Gary J.D. Wurmser A.E. Bonangelino C.J. Weisman L.S. Emr S.D. Fab1p is essential for PtdIns(3)P 5-kinase activity and the maintenance of vacuolar size and membrane homeostasis. J. Cell Biol. 1998; 143: 65-79 Crossref PubMed Scopus (338) Google Scholar . Fab1p has a C-terminal phosphatidylinositol phosphate kinase domain, and an N-terminal RING FYVE domain, a type of zinc finger thought to bind specifically to PtdIns(3)P. Fab1p deletion strains fail to produce PtdIns(3,5)P2 and have elevated PtdIns(3)P. These cells have a grotesquely distended vacuole lacking proper acidification. Trafficking from the Golgi apparatus to the vacuole [which requires PtdIns(3)P] is intact, and so it appears that PtdIns(3,5)P2 is required at a later step, perhaps to recycle membrane to the Golgi or internalize it into the vacuole. Fab1p seems to require at least one other protein, Vac7p, for activity, but sadly Vac7p has little homology to any known proteins. Working out its functions, as well as those of PtdIns(3,5)P2 itself, is sure to be under way soon.