Phosphatidylinositol transfer protein required for ATP-dependent priming of Ca2+-activated secretion

Hay, Jesse; Martin, Thomas F.J.

doi:10.1038/366572a0

Cited by 349 publications

(262 citation statements)

References 30 publications

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“…to PI(4,5)P 2 -are required for the reconstitution of Ca 2+ -dependent dense-core vesicle secretion [43][44][45] . Two findings suggest that these results may be directly relevant to synaptic vesicle exocytosis.…”

Section: Flippasementioning

confidence: 99%

A neuroscientist's guide to lipidomics

2007

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| Nerve cells mould the lipid fabric of their membranes to ease vesicle fusion, regulate ion fluxes and create specialized microenvironments that contribute to cellular communication. The chemical diversity of membrane lipids controls protein traffic, facilitates recognition between cells and leads to the production of hundreds of molecules that carry information both within and across cells. With so many roles, it is no wonder that lipids make up half of the human brain in dry weight. The objective of neural lipidomics is to understand how these molecules work together; this difficult task will greatly benefit from technical advances that might enable the testing of emerging hypotheses.

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Section: Flippasementioning

confidence: 99%

A neuroscientist's guide to lipidomics

2007

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“…Phosphoinositides are essential in several aspects of membrane traffic [9,10], and PITP has been found to be required. PITP is required for the exocytosis of secretory granules [11,12] and budding of secretory vesicles from the trans-Golgi network [13,14]. Many phosphorylated inositol lipids are synthesized on demand, directly from PtdIns, at different sites in the cell.…”

Section: Introductionmentioning

confidence: 99%

“…This includes both vesicle formation and exocytosis [11][12][13]. Dictyostelium systems have more in common with mammalian systems with regard to their use of phosphoinositides in signalling cascades [35].…”

mentioning

confidence: 99%

Purification and cloning of phosphatidylinositol transfer proteins from Dictyostelium discoideum: homologues of both mammalian PITPs and Saccharomyces cerevisiae Sec14p are found in the same cell

Swigart

Insall

Cockcroft

2000

Biochemical Journal

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Soluble phosphatidylinositol transfer proteins (PITPs) have important roles in lipid-mediated signalling as well as in membrane traffic. Two PITPs (α and β) have been cloned from mammalian cells, which are unrelated in sequence to yeast PITP (the product of the SEC14 gene). However, all three PITPs can perform interchangeably to reconstitute function in mammalian cells. We have now purified the major PITP from the cytoplasm of Dictyostelium discoideum and cloned the gene. This protein, DdPITP1, is homologous with mammalian PITPα and PITPβ. We have also cloned a second gene (DdPITP2) related in sequence to DdPITP1. In addition, an independently cloned cDNA encodes a relative of the SEC14 family of yeast PITPs. DdPITP1, DdPITP2 and DdSec14 proteins were all able to mediate the transfer of PtdIns from one membrane compartment to another; they thus exhibited the hallmark of PITPs. Secondly, all three PITPs were able to rescue phospholipase C-mediated phosphoinositide hydrolysis in PITP-depleted HL60 cells, indicating that all three PITPs were capable of stimulating phosphoinositide synthesis. The identification of PITPs related to both mammalian PITPs and yeast Sec14p in a single organism will provide a unique opportunity to examine the functions of this class of protein with genetic approaches.

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“…The inhibition of Ca 2ϩ -dependent catecholamine release after depletion of phosphatidylinositol highlighted the role of phosphoinositides during the secretory events (Eberhard et al, 1990). Moreover, phosphatidylinositol transfer protein and phosphatidylinositol-4-phosphate 5 kinase (PI4P5K) were shown to be required for the ATP-dependent priming of secretory granules in PC12 cells (Hay and Martin, 1993;Hay et al, 1995). In addition, phosphatidylinositol 4-kinase (PI4K), an integral membrane protein of chromaffin granules and synaptic vesicles, is required for their exocytosis (Wiedemann et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

Phosphatidylinositol 3-Kinase C2α Is Essential for ATP-dependent Priming of Neurosecretory Granule Exocytosis

Meunier

Osborne

Hammond

et al. 2005

MBoC

102

108

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Neurotransmitter release and hormonal secretion are highly regulated processes culminating in the calcium-dependent fusion of secretory vesicles with the plasma membrane. Here, we have identified a role for phosphatidylinositol 3-kinase C2␣ (PI3K-C2␣) and its main catalytic product, PtdIns3P, in regulated exocytosis. In neuroendocrine cells, PI3K-C2␣ is present on a subpopulation of mature secretory granules. Impairment of PI3K-C2␣ function specifically inhibits the ATP-dependent priming phase of exocytosis. Overexpression of wild-type PI3K-C2␣ enhanced secretion, whereas transfection of PC12 cells with a catalytically inactive PI3K-C2␣ mutant or a 2xFYVE domain sequestering PtdIns3P abolished secretion. Based on these results, we propose that production of PtdIns3P by PI3K-C2␣ is required for acquisition of fusion competence in neurosecretion. INTRODUCTIONThe analysis of the molecular mechanism controlling neuroexocytosis has been greatly helped by studies on neurosecretory cells (Dunn and Holz, 1983;Sarafian et al., 1987;Martin and Walent, 1989;Monck and Fernandez, 1994;Rettig and Neher, 2002). Early work has shed light on two major steps consisting of the reversible ATP-dependent priming of docked granules followed by their Ca 2ϩ -driven fusion with the plasma membrane and release of the granule content (Holz et al., 1989;Hay and Martin, 1992). The spatiotemporal control of intracellular Ca 2ϩ concentration together with capacitance measurements has allowed the identification of distinct pools of chromaffin granules involved in these distinct steps (Rettig and Neher, 2002). Further electrophysiological and biochemical approaches, such as the reconstitution of secretion in permeabilized neurosecretory cells (Martin and Walent, 1989), have highlighted the role of key factors involved in these two processes. Cytosolic and membrane proteins have been linked to priming and fusion, including the mammalian orthologues of the Caenorhabditis elegans UNC13 and UNC18 gene products, synaptotagmins, and members of the SNARE family and associated proteins (Jahn and Sudhof, 1999;Burgoyne et al., 2001;Brose and Rosenmund, 2002;Rettig and Neher, 2002).In contrast, less is known about the contribution of lipid dynamics during these processes with the exception of phosphatidic acid and phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P 2 ]. The former is produced by phospholipase D, which is essential for secretion in neurons (Humeau et al., 2001) and in neuroendocrine cells . The inhibition of Ca 2ϩ -dependent catecholamine release after depletion of phosphatidylinositol highlighted the role of phosphoinositides during the secretory events (Eberhard et al., 1990). Moreover, phosphatidylinositol transfer protein and phosphatidylinositol-4-phosphate 5 kinase (PI4P5K) were shown to be required for the ATP-dependent priming of secretory granules in PC12 cells (Hay and Martin, 1993;Hay et al., 1995). In addition, phosphatidylinositol 4-kinase (PI4K), an integral membrane protein of chromaffin granules and synaptic vesicles, is r...

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Phosphatidylinositol transfer protein required for ATP-dependent priming of Ca2+-activated secretion

Cited by 349 publications

References 30 publications

A neuroscientist's guide to lipidomics

A neuroscientist's guide to lipidomics

Purification and cloning of phosphatidylinositol transfer proteins from Dictyostelium discoideum: homologues of both mammalian PITPs and Saccharomyces cerevisiae Sec14p are found in the same cell

Phosphatidylinositol 3-Kinase C2α Is Essential for ATP-dependent Priming of Neurosecretory Granule Exocytosis

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