Role of Phospholipase D Activation in Nervous System Physiology and Pathophysiology

Klein, Jochen; Chalifa, Vered; Liscovitch, Mordechai; Löffelholz, K.

doi:10.1046/j.1471-4159.1995.65041445.x

Cited by 110 publications

(50 citation statements)

References 59 publications

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“…In several cell types, the activity of PKC is required for the activation of PLD by receptor agonists (Thompson et al, 1993;Exton, 1994;Klein et al, 1995). As mentioned above, El stimulates the activities of a PLA 2 and a phosphoinositide-specific PLC by acting on nonselective El receptors (Mann et al, 1991;Tencé et a!., 1992; present results).…”

Section: Role Of Pkc In the El-i -Induced Activation Of Pldsupporting

confidence: 65%

“…Several tissues contain a phosphatidate phosphohydrolase that converts PA into diacylglycerol (DAG), the endogenous activator of PKC. By generating PA, PLD may induce long-term increases in DAG that may be involved in the activation of slow processes such as cell proliferation and differentiation (Thompson et al, 1993;Exton, 1994;Klein et al, 1995). PA may also be metabolized into lysophosphatidic acid, a novel lipid intercellular messenger (reviewed by Moolenaar, 1994) that, for instance, can stimulate tyrosine phosphorylation (MacLees et al, 1995) and cell proliferation or regulate gap-junctional communications (Hii et a!., 1994).…”

Section: Introductionmentioning

confidence: 99%

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Endothelin Stimulates Phospholipase D in Striatal Astrocytes

Desagher

Cordier

Głowiński

et al. 1997

Journal of Neurochemistry

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Acute treatment with PMA also stimulated PLD through a protein kinase C-dependent process. However, the ET-1 and PMA responses were additive. Furthermore, the ET-1 -evoked response, contrary to that of PMA, totally depended on the presence of extracellular calcium. These results suggest that at least two distinct mechanisms are involved in the control of PLO activity in striatal astrocytes. Finally, ET-1, ET-3, and PMA also stimulated PLO in astrocytes from the mesencephalon, the cerebral cortex, and the hippocampus.

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Section: Role Of Pkc In the El-i -Induced Activation Of Pldsupporting

confidence: 65%

Section: Introductionmentioning

confidence: 99%

Endothelin Stimulates Phospholipase D in Striatal Astrocytes

Desagher

Cordier

Głowiński

et al. 1997

Journal of Neurochemistry

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“…Muscarinic stimulation is well documented to activate PLD in various cell types, including SY5Y cells, although distinctions have not been characterized between the PLD 1 and PLD 2 isoforms (26,27). PLD 2 is a constitutively active isoform of PLD that is localized primarily along the plasma membrane (9).…”

Section: Resultsmentioning

confidence: 99%

Muscarinic Receptor Stimulation Induces Translocation of an α-Synuclein Oligomer from Plasma Membrane to a Light Vesicle Fraction in Cytoplasm

Leng¹,

Chase²,

Bennett³

2001

Journal of Biological Chemistry

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The close correspondence between the distribution of brain ␣-synuclein and that of muscarinic M 1 and M 3 receptors suggests a role for this protein in cholinergic transmission. We thus examined the effect of muscarinic stimulation on ␣-synuclein in SH-SY5Y, a human dopaminergic cell line that expresses this protein. Under basal conditions, ␣-synuclein was detected in all subcellular compartments isolated as follows: plasma membrane, cytoplasm, nucleus, and two vesicle fractions. The lipid fractions contained only a 45-kDa ␣-synuclein oligomer, whereas the cytoplasmic and nuclear fractions contained both the oligomer and the monomer. This finding suggests ␣-synuclein exists physiologically as a lipid-bound oligomer and a soluble monomer. Muscarinic stimulation by carbachol reduced the ␣-synuclein oligomer in plasma membrane over a 30-min period, with a concomitant increase of both the oligomer and the monomer in the cytoplasmic fraction. The oligomer was associated with a light vesicle fraction in cytoplasm that contains uncoated endocytotic vesicles. The carbachol-induced alteration of ␣-synuclein was blocked by atropine. Translocation of the ␣-synuclein oligomer in response to carbachol stimulation corresponds closely with the time course of ligandstimulated muscarinic receptor endocytosis. The data suggest that the muscarine receptor stimulated release of the ␣-synuclein oligomer from plasma membrane, and its subsequent association with the endocytotic vesicle fraction may have a role in muscarine receptor endocytosis. We propose that its function may be a transient release of membrane-bound phospholipase D 2 from ␣-synuclein inhibition, thus allowing this lipase to participate in muscarinic receptor endocytosis.The neuronal protein ␣-synuclein, recently implicated in the pathogenesis of Parkinson's disease (1-3), has a brain distribution closely matching that of muscarinic M 1 and M 3 receptors and the muscarine receptor-linked enzymes phospholipase C and protein kinase C (4). The proximity of ␣-synuclein to brain muscarinic receptors and related enzymes suggests that this protein could contribute to cholinergic function. To evaluate this possibility, we investigated the effect of muscarinic receptor stimulation by the cholinergic agonist carbachol on the subcellular distribution of endogenous ␣-synuclein in the human neuroblastoma cell line SH-SY5Y. This dopaminergic cell line shares many properties with dopamine neurons of substantia nigra pars compacta, the major locus of neurodegeneration in Parkinson's disease, including the expression of M 1 and M 3 receptors (5). We now report that carbachol induces a translocation of a 45-kDa ␣-synuclein oligomer from plasma membrane to a light vesicle fraction in cytoplasm, with a time course and subcellular localization matching that of muscarinic receptors during carbachol-stimulated endocytosis. Previously, synucleins have been demonstrated to be endogenous inhibitors of phospholipase D 2 (PLD 2 ) 1 (6). Furthermore, activation of PLD isoforms, including PLD 2 , ...

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“…choline). PA and its derivatives diacylglycerol (DAG) and lysophosphatidic acid (LPA) are important signaling molecules whereas choline is the precursor to the common neurotransmitter acetylcholine [1]. Two distinct isoforms of PLD, denoted PLD1 and PLD2, have been identified from several mammalian sources [2][3][4][5][6][7][8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

The uncovering of a novel regulatory mechanism for PLD2: Formation of a ternary complex with protein tyrosine phosphatase PTP1B and growth factor receptor-bound protein GRB2

Horn¹,

López²,

Miller³

et al. 2005

Biochemical and Biophysical Research Communications

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The regulation of PLD2 activation is poorly understood at present. Transient transfection of COS-7 with a mycPLD2 construct results in elevated levels of PLD2 enzymatic activity and tyrosyl phosphorylation. To investigate whether this phosphorylation affects PLD2 enzymatic activity, anti-myc immunoprecipitates were treated with recombinant protein tyrosine phosphatase PTP1B. Surprisingly, lipase activity and PY levels both increased over a range of PTP1B concentrations. These increases occurred in parallel to a measurable PTP1B-associated phosphatase activity. Inhibitor studies demonstrated that an EGF-receptor type kinase is involved in phosphorylation. In a COS-7 cell line created in the laboratory that stably expressed myc-PLD2, PTP1B induced a robust (>6-fold) augmentation of myc-PLD2 phosphotyrosine content. The addition of growth factor receptor-bound protein 2 (Grb2) to cell extracts also elevated PY levels of myc-PLD (>10-fold). Systematic co-immunoprecipitation-immunoblotting experiments pointed at a physical association between PLD2, Grb2 and PTP1B in both physiological conditions and in overexpressed cells. This is the first report of a demonstration of the mammalian isoform PLD2 existing in a ternary complex with a protein tyrosine phosphatase, PTP1b, and the docking protein Grb2 which greatly enhances tyrosyl phosphorylation of the lipase.

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Role of Phospholipase D Activation in Nervous System Physiology and Pathophysiology

Cited by 110 publications

References 59 publications

Endothelin Stimulates Phospholipase D in Striatal Astrocytes

Endothelin Stimulates Phospholipase D in Striatal Astrocytes

Muscarinic Receptor Stimulation Induces Translocation of an α-Synuclein Oligomer from Plasma Membrane to a Light Vesicle Fraction in Cytoplasm

The uncovering of a novel regulatory mechanism for PLD2: Formation of a ternary complex with protein tyrosine phosphatase PTP1B and growth factor receptor-bound protein GRB2

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