A MAMMALIAN GOLGI SEC1P-LIKE PROTEIN, MVPS45

Our understanding of lysosomal biogenesis and general vesicular transp ort in animal cells has been greatly enhanced by studies of vacuolar b iogenesis in yeast. Genetic screens have identified a number of protei ns that play direct roles in the proper sorting of vacuolar hydrolases . These include t-SNARE (soluble N-ethylmaleimide-sensitive factor att achment protein receptor) proteins and Sec1p-like proteins, which have recently been implicated as key regulators of vesicle fusion. In this study we have extended these observations in yeast and have isolated and characterized a novel member of the Sec1p-like family of proteins from mammalian cells, mVps45. mVps45 shares a high level of identity w ith the Saccharomyces cerevisiae Sec1p-like protein Vps45p that is bel ieved to function with the t-SNARE Pep12p in the fusion of Gels-derive d transport vesicles with a prevacuolar compartment, We found that mVp s45 is a ubiquitously expressed peripheral membrane protein that local ized to perinuclear Gels-like and trans-Golgi network compartments in Chinese hamster every cells. We found that mVps45 could bind specifica lly to yeast Pep12p and to the mammalian Pep12p-like protein, syntaxin 6, in vitro.