title: 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.
authors.affiliation: Department of Cell and Developmental Biology, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7090, USA. vytas@med.unc.edu
authors.forename: Vytas A
authors.initials: VA
authors.lastname: Bankaitis
authors.forename: Scott
authors.initials: S
authors.lastname: Phillips
authors.forename: Lora
authors.initials: L
authors.lastname: Yanagisawa
authors.forename: Xinmin
authors.initials: X
authors.lastname: Li
authors.forename: Sheri
authors.initials: S
authors.lastname: Routt
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Xie
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D020690:GTPase-Activating Proteins / Q000502:physiology; D006056:Golgi Apparatus / Q000502:physiology; D050356:Lipid Metabolism / Q000502:physiology; D008565:Membrane Proteins / Q000502:physiology; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D049294:Phospholipid Transfer Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D011987:Receptors, Steroid; D012441:Saccharomyces cerevisiae / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D000098825:Oxysterol Binding Proteins
chemical_list: D020690:GTPase-Activating Proteins; D008565:Membrane Proteins; D049294:Phospholipid Transfer Proteins; D011987:Receptors, Steroid; D029701:Saccharomyces cerevisiae Proteins; C087901:KES1 protein, S cerevisiae; D000098825:Oxysterol Binding Proteins; C493468:Pitpn protein, mouse; C483438:SEC14 protein, S cerevisiae