The interface between phosphatidylinositol transfer protein function and phosphoinositide signaling in higher eukaryotes

• Published in: Journal of lipid research Vol. 60; no. 2; pp. 242 - 268
• Main Authors: Grabon, Aby, Bankaitis, Vytas A., McDermott, Mark I.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2019; The American Society for Biochemistry and Molecular Biology; Elsevier
• Series: Thematic Review Series: The Role of Phosphoinositides in Signaling and Disease
• Subjects: Animals; cell signaling; diseases; Eukaryota - cytology; Eukaryota - metabolism; Humans; lipid and membrane trafficking; lipid signaling; lipids • membranes; Phosphatidylinositols - metabolism; Phospholipid Transfer Proteins - chemistry; Phospholipid Transfer Proteins - metabolism; Signal Transduction; Thematic Review Series: The Role of Phosphoinositides in Signaling and Disease; lipid and membrane trafficking; diseases; lipid signaling; cell signaling; lipids • membranes
• ISSN: 0022-2275; 1539-7262; 1539-7262
• DOI: 10.1194/jlr.R089730

Phosphoinositides are key regulators of a large number of diverse cellular processes that include membrane trafficking, plasma membrane receptor signaling, cell proliferation, and transcription. How a small number of chemically distinct phosphoinositide signals are functionally amplified to exert specific control over such a diverse set of biological outcomes remains incompletely understood. To this end, a novel mechanism is now taking shape, and it involves phosphatidylinositol (PtdIns) transfer proteins (PITPs). The concept that PITPs exert instructive regulation of PtdIns 4-OH kinase activities and thereby channel phosphoinositide production to specific biological outcomes, identifies PITPs as central factors in the diversification of phosphoinositide signaling. There are two evolutionarily distinct families of PITPs: the Sec14-like and the StAR-related lipid transfer domain (START)-like families. Of these two families, the START-like PITPs are the least understood. Herein, we review recent insights into the biochemical, cellular, and physiological function of both PITP families with greater emphasis on the START-like PITPs, and we discuss the underlying mechanisms through which these proteins regulate phosphoinositide signaling and how these actions translate to human health and disease.