Glycerylphosphorylcholine diesterase activity of nervous tissue

Webster, G. R.; Marples, Elizabeth A.; Thompson, R. H. S.

doi:10.1042/bj0650374

Cited by 57 publications

(17 citation statements)

References 8 publications

(3 reference statements)

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“…In mammals, no GP-PDE has been cloned up to now. However, GP-PDE enzymatic activity with GPC (GPC-PDE, EC 3.1.4.2), glycerophosphoethanolamine, or glycerophosphoinositol (glycerophosphoinositol PDE, EC 3.1.4.44) as substrates has been observed in a number of mammalian tissues including liver (25,26), brain (27), and kidney (28). Preliminary studies on the biochemical properties of the enzyme suggest that multiple enzymes may be responsible for the activity (29,30).…”

Section: Discussionmentioning

confidence: 99%

MIR16, a putative membrane glycerophosphodiester phosphodiesterase, interacts with RGS16

Zheng

Chen

Farquhar

2000

Proc. Natl. Acad. Sci. U.S.A.

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We have identified the protein MIR16 (for Membrane Interacting protein of RGS16) from a yeast two-hybrid screen by using RGS16 as bait. MIR16 shares strong homology with bacterial glycerophosphodiester phosphodiesterases. It interacts with RGS16 and, more weakly, with several other selected RGS proteins. Analysis of deletion mutants showed that the N-terminal region of the RGS domain in RGS16 is required for its interaction with MIR16. MIR16 is an integral membrane glycoprotein, because it remained associated with membrane fractions after alkaline treatment and because, in some cells, it is sensitive to digestion with endoglycosidase H. By immunofluorescence and immunoelectron microscopy, MIR16 was localized on the plasma membrane in liver and kidney and on intracellular membranes in rat pituitary and cultured pituitary cells. MIR16 represents the only integral membrane protein identified thus far to interact with an RGS domain and, to our knowledge, is the only mammalian glycerophosphodiester phosphodiesterase that has been cloned. The putative enzymatic activity of MIR16 and its interaction with RGS16 suggest that it may play important roles in lipid metabolism and in G protein signaling.G protein ͉ integral membrane protein ͉ lipid metabolism H eterotrimeric G proteins transduce a variety of extracellular signals from G protein-coupled receptors to downstream G protein effectors (1, 2). Recently, a protein family, the RGS proteins (for Regulator of G protein Signaling), has been discovered; these proteins regulate G␣ subunits by acting as GTPase activating proteins (3-5). To date, at least 24 distinct RGS proteins have been found in mammals, but information on the connections of RGS proteins to specific signaling pathways and on the functional roles of RGS proteins in specific biological systems is still limited (3, 4).We have been interested in defining the G protein-mediated signaling pathways associated with intracellular membranes (6, 7). Previously, we identified GAIP (G␣ interacting protein), one of the founding members of the RGS protein family, and localized it to clathrin-coated vesicles in pituitary cells and hepatocytes, among others (6). Besides GAIP, additional RGS proteins have also been found in pituitary, liver, and other secretory cells (3). We have chosen RGS16 (ref. 8; ref. 9; ref. 10) for further study, because our interests focus on secretory cells and because RGS16 was shown to be highly expressed in mouse pituitary and liver (8). RGS16 has been shown to be a GTPase activating protein for members of the G␣i family in vitro (9, 11). However, little information is available concerning the interaction of RGS16 with molecules other than G␣ subunits.To define further signaling pathways involving RGS16, we used the yeast two-hybrid system to identify proteins that interact with RGS16. Herein, we report the discovery of an integral membrane protein MIR16 (for Membrane Interacting protein of RGS16), identified by screening a pituitary cell cDNA library with RGS16 as bait. Sequence analysis ind...

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Section: Discussionmentioning

confidence: 99%

MIR16, a putative membrane glycerophosphodiester phosphodiesterase, interacts with RGS16

Zheng

Chen

Farquhar

2000

Proc. Natl. Acad. Sci. U.S.A.

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“…That the stimulation of PLA2 may, by enhancing fatty acid accumulation, activate PLD and thus accelerate the liberation of choline from PC is suggested by the presence of elevated fatty acid and choline concentrations in the hypoxic brain (100). Lysophosphatidylcholine (LPC) formed by PLA1 and PLA2 can be further metabolized to free choline by lysophospholipase D (LPLD) (101) or hydrolyzed to glycerophosphocholine (GPCh) by a lysophospholipase (LPL) (102); GPCh is then converted to PCh by GPCh cholinephospho-hydrolase (103) or to free choline by GPCh diesterase (104), and the PCh is hydrolyzed to free choline by alkaline phosphatase (87,105).…”

Section: Factors Supplying Choline To the Brain Neuronsmentioning

confidence: 99%

Choline and Cholinergic Neurons

Blusztajn

Wurtman

1983

Science

415

151

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Mammalian neurons can synthesize choline by methylating phosphatidylethanolamine and hydrolyzing the resulting phosphatidylcholine. This process is stimulated by catecholamines. The phosphatidylethanolamine is synthesized in part from phosphatidylserine; hence the amino acids methionine (acting after conversion to S-adenosylmethionine) and serine can be the ultimate precursors of choline. Brain choline concentrations are generally higher than plasma concentrations, but depend on plasma concentrations because of the kinetic characteristics of the blood-brain-barrier transport system. When cholinergic neurons are activated, acetylcholine release can be enhanced by treatments that increase plasma choline (for example, consumption of certain foods).

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“…Thus, it is unlikely that PtdCho was hydrolyzed by a phospholipase C (phosphatidylcholine cholinephosphohydrolase, EC 3.1.4.3) or by a multienzymatic pathway consisting of phospholipase A2 (phosphatidylcholine 2-acylhydrolase, EC 3.1.1.4), lysophospholipase (2-lysophosphatidylcholine acylhydrolase, EC 3.1.1.5), and glycerophosphocholine cholinephosphodiesterase (sn-glycero-3-phosphocholine cholinephosphohydrolase, EC 3.1.4.38) (26). Rather, if GroPCho were generated by phospholipase A2 and lysophospholipase, it could then be hydrolyzed directly to choline by glycerophosphocholine phosphodiesterase (sn-glycero-3-phosphocholine glycerophosphohydrolase, EC 3.1.4.2) (27). Alternatively, PtdCho could be hydrolyzed directly to choline by a phospholipase D (phosphatidylcholine phosphatidohydrolase, EC 3.1.4.4), an enzyme activated by certain fatty acids (28).…”

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confidence: 99%