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The Diverse Functions of Phosphatidylinositol Transfer Proteins

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Phosphoinositides and Disease

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 362))

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.

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Abbreviations

PPIs:

Phosphoinositides

PI:

Phosphatidylinositol

PITP:

Phosphatidylinositol transfer protein

RdgB:

Retinal degeneration type B

PC:

Phosphatidylcholine

PI(4,5)P2 :

Phosphatidylinositol (4,5) bisphosphate

PA:

Phosphatidic acid

HAD:

Haloacid dehalogenase

PCTP:

PC transfer protein

HL60:

Human promyelocytic leukemia cells

DCC:

Deleted in colon cancer

COP-1:

Coat protein complex-1

SRC:

Subrhabdomeric cisternae

PIS:

PI synthase

CDS:

CDP-DAG synthase

DAG:

Diacylglycerol

ERG:

Electroretinogram

ATRAP (alt. name AGTRAP):

Angiotensin II receptor-associated protein

AT1R:

Angiotensin II Type 1 receptor

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  1. Department of Neuroscience, Physiology and Pharmacology, Division of Biosciences, University College London, London, WC1E 6JJ, UK

    Shamshad Cockcroft

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  1. CTR DIABETES BARTS, Queen Mary University of London, UK, NEWARK ST 4, LONDON E1 2AT, United Kingdom

    MARCO FALASCA

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Cockcroft, S. (2012). The Diverse Functions of Phosphatidylinositol Transfer Proteins. In: FALASCA, M. (eds) Phosphoinositides and Disease. Current Topics in Microbiology and Immunology, vol 362. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-5025-8_9

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