The Diverse Functions of Phosphatidylinositol Transfer Proteins

Abstract

Phosphatidylinositol transfer proteins (PITPs), comprising five members in the human genome are implicated in the non-vesicular traffic of phosphatidylinositol (PI) between intracellular membranes and the plasma membrane. Three members of the PITP family (PITPα, PITPβ, and RdgBβ (retinal degeneration type B) alt. name PITPNC1) are present as single domain proteins and two (RdgBαI and RdgBαII alt. name PITPNM1 and PITPNM2) are present as multi-domain proteins with the PITP domain located at the N-terminus. The hallmark of PITP proteins is to extract PI molecules from a membrane, sequester in its binding pocket and deposit the lipid to membranes. PITPs regulate the synthesis of phosphoinositides (PPIs) either by delivery of the substrate, PI to specific membrane compartments or by potentiating the activities of the lipid kinases, or both. In the light of recent studies, we propose that PITPs are regulators of phosphoinositide pathways by recruitment to membranes through specific protein interactions to promote molecular exchange between closely opposed membranes i.e., at membrane contact sites. Individual PITP proteins play highly specific roles in many biological processes including neurite outgrowth, membrane traffic, cytokinesis, and sensory transduction in mammals as well as in the model organisms, Drosophila, Caenorhabditis elegans, and zebrafish. The common requirement for the diverse functions for all PITPs is their ability to bind PI and coupling its function to phosphoinositide-dependent pathways.