Bankaitis Vytas A, Phillips Scott, Yanagisawa Lora, Li Xinmin, Routt Sheri, Xie Zhigang
Department of Cell and Developmental Biology, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7090, USA.
Adv Enzyme Regul. 2005;45:155-70. doi: 10.1016/j.advenzreg.2005.02.014. Epub 2005 Aug 22.
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.
磷脂酰肌醇转移蛋白（PITPs）调节脂质代谢与细胞功能之间的界面，但这种调节的基本性质尚不清楚。酵母和小鼠研究表明，单个PITPs与特定细胞活动存在严格的耦合关系，但这些特异性在PITP活性的体外模型中却不明显。我们认为，描绘PITP的功能需要继续应用此处总结的遗传方法。未来致力于增强我们对Sec14p样蛋白和后生动物PITPs作用机制理解的研究是有价值的目标，原因有三。首先，越来越清楚的是，PITPs作用于涉及脂质和蛋白质运输、磷脂生物合成以及极化膜生长的重要生物学界面。由于这些界面不仅对细胞功能至关重要，而且对发育过程也至关重要，因此PITPs在多细胞生物发育中的功能是一个特别有吸引力但基本上尚未开发的研究领域。其次，酵母研究表明Sec14p样PITPs与普遍存在但完全未表征的真核蛋白成员（如OSBP家族成员）之间存在功能联系。最后，PITPs与疾病的联系已经很明显，因为PITP缺陷是哺乳动物神经退行性、葡萄糖稳态和胃肠道疾病新机制的基础。鉴于Sec14p样蛋白对哺乳动物细胞PITP补充的贡献完全未被研究，并且哺乳动物基因组编码许多此类蛋白，我们预计这些进展将直接并积极地影响我们对这些疾病分子基础的理解。
