Phosphatidylinositol transfer protein function in the yeast Saccharomyces cerevisiae

Abstract

PITPs regulate the interface between lipid metabolism and cellular functions, but the fundamental nature of this regulation is not understood. Yeast and mouse studies demonstrate strict coupling of individual PITPs to specific cellular activities, but the invisibility of these specificities in in vitro models for PITP activity is remarkable. In our opinion, delineation of PITP functions requires the continued application of genetic approaches such as those summarized here. Future studies dedicated to enhancing our understanding of the mechanisms of action of Sec14p-like and metazoan PITPs are worthy goals for three reasons. First, it is becoming abundantly clear that PITPs act at important biological interfaces that involve lipid and protein trafficking, phospholipid biosynthesis and polarized membrane growth. Because these interfaces are critical not only to cellular functions, but also to developmental processes, the function of PITPs in development of multicellular organisms is a particularly attractive area of research that remains essentially untapped. Second, the yeast studies indicate functional linkages between Sec14p-like PITPs and members of ubiquitous but entirely uncharacterized eukaryotic proteins such as OSBP family members. Finally, the link of PITPs to disease is already clear since PITP deficiencies lie at the foundation of novel mechanisms of neurodegenerative, glucose homeostatic and gastrointestinal disorders in mammals. Given that the contribution of Sec14p-like proteins to the PITP complement of mammalian cells is completely uninvestigated, and that the mammalian genome encodes many proteins of this class, we anticipate such advances will directly and positively impact our understanding of the molecular basis of such diseases.