Inositol phospholipids in membrane function

Michell, Robert H.

doi:10.1016/0968-0004(79)90443-2

Cited by 275 publications

(83 citation statements)

References 25 publications

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“…In the past 30 years, more than 30 biological phenomena have been correlated with increased turnover of PtdIns (3)(4)(5). The data in this paper show that phagocytosis of complement-opsonized liposomes (Fig.…”

Section: Discussionsupporting

confidence: 48%

“…Since that initial observation, "PtdIns responses" (enhanced PtdIns turnover) have been reported in a wide variety of tissues and cells and have been correlated with numerous stimuli modulating different cell functions (reviewed in refs. [2][3][4][5][6][7]. Despite the voluminous literature in this field, the molecular basis of the PtdIns response, as well as its exact mechanism and function, have not been completely elucidated (2)(3)(4)(5)(6)(7).…”

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confidence: 99%

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Suppression of phagocytic function and phospholipid metabolism in macrophages by phosphatidylinositol liposomes.

Wassef¹,

Roerdink²,

Richardson³

et al. 1984

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

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Increased phagocytosis of complement-opsonized vesicles was accompanied by increased phosphatidylinositol (Ptdlns) turnover in murine macrophages. However when PtdIns was also present as one of the lipids in the opsonized liposomes, it reduced both phagocytosis and stimulation of endogenous Ptdlns turnover. These suppressive effects did not occur with liposomes containing PtdIns phosphate (PtdIns-P). When a monoclonal IgM "anti-PtdIns-P" antibody that bound to inositol phosphate was substituted for antigalactosyl ceramide antibodies for activating complement in the opsonizing process, eflhanced phagocytosis occurred normally but increased cellular PtdIns turnover did not occur. Therefore the data show that, although PtdIns-P cannot replace PtdIns for suppressing Ptdlns turnover, Ptdlns-P can be induced to be suppressive after specific binding to an antibody that recognizes inositol phosphate. We conclude that ingestion of complement-opsonized liposomes by macrophages and complement-induced turnover of cellular PtdIns are separate but related phenomena that can be independently modulated by the polar group of liposomal Ptdlns.In 1953 Hokin and Hokin (1) observed that acetylcholine caused an enhancement of phosphatidylinositol (Ptdlns) metabolism in pancreatic slices. This suggested that Ptdlns might have a special function in the cell response to external stimulation by acetylcholine. Since that initial observation, "PtdIns responses" (enhanced PtdIns turnover) have been reported in a wide variety of tissues and cells and have been correlated with numerous stimuli modulating different cell functions (reviewed in refs. 2-7). Despite the voluminous literature in this field, the molecular basis of the PtdIns response, as well as its exact mechanism and function, have not been completely elucidated (2-7).The original purpose of the present study was to determine whether a Ptdlns response would appear during the course of complement-opsonized phagocytosis of liposomes. It was felt that this observation would be a natural step in a continuing investigation of complement-induced ingestion of liposomes by macrophages (8). Although a PtdIns response was indeed found, in the course of this work we also made a surprising discovery that the PtdIns response was exquisitely sensitive to the presence of exogenous PtdIns in the opsonized liposomes and the PtdIns response was suppressed when the liposomes contained Ptdlns. It occurred to us that this observation might have broad implications because PtdIns that is initially external to the cell had not been used previously to study modulation of intracellular Ptdlns turnover.In this paper we report (i) that both phagocytosis of liposomes and intracellular PtdIns turnover are enhanced by complement opsonization of the liposomes, (ii) that incubation of liposomal PtdIns with macrophages strongly suppresses both the phagocytosis of complement-opsonized liposomes and intracellular PtdIns turnover, and (iii) that complement-induced phagocytosis and increased PtdIns turnover in...

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Section: Discussionsupporting

confidence: 48%

mentioning

confidence: 99%

Suppression of phagocytic function and phospholipid metabolism in macrophages by phosphatidylinositol liposomes.

Wassef¹,

Roerdink²,

Richardson³

et al. 1984

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

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“…In the presence of diacylglycerol, the enzyme becomes associated with membranes and phosphorylates endogenous substrates (374). The binding of many different hormones and neurotransmitters to specific classes of receptors results in increased phosphatidylinositol turnover (375), so the enzyme may be an important mediator of hormone and transmitter action.…”

Section: Calmodulin Calcineurin Interactions-calmodulin the Virtuallmentioning

confidence: 99%

A Molecular Description of Nerve Terminal Function

Reichardt¹,

Kelly²

1983

Annu. Rev. Biochem.

226

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The nerve terminal is a specialized region of a neuron, separated from the neuronal soma by an axon that can be exceedingly long, whose function is to release neurotransmitter when stimulated by an electrical signal carried by the axon. In this review, we describe the enzymes, channels, and other proteins presently thought to be important in nerve terminal function. Recent progress in the area has been so dramatic that it is becoming possible to relate simple changes in behavior to modifications of defined proteins in particular nerve terminals.Neurotransmitters are stored in synaptic vesicles and are released by fusion of these vesicles to the plasma membrane. Vesicle fusion is triggered by Ca 2+ -influx through specific Ca 2+ channels that open in response to depolarization of the plasma membrane and is terminated by the disappearance of Ca 2+ from the vicinities of the active zones. The voltage signal that opens the Ca 2+ gates is not constant, but also subject to regulation. The key elements are the Na + and K + channels in the nerve terminal. These channels are localized to distinct regions of many neurons and different neurons have different quantities of the different channel types. The voltage sensitive Na + channel is responsible for depolarizing the membrane. This channel has recently been purified and reconstituted in artificial membranes, so many of its properties are known. K + channels are responsible for repolarizing the membrane. Several K + channels have been identified: some activated by voltage, some by intracellular Ca 2+ and others by neurotransmitters. The properties of several of these have recently been shown to be altered by cAMP-dependent protein kinases, resulting in long-term changes in neuronal activity and the efficiency of synaptic transmission. The voltage-dependent Ca 2+ channels can also be modified by cAMP-dependent protein kinases. Many of the neurotransmitters and hormones that modulate the efficiency of transmitter release apparently do so by modifying the Ca 2+ channels. Much of the recent progress in molecular studies on the K + and Ca 2+ channels has been made possible by a dramatic new technique called "patch clamping" that permits individual ion channels to be examined on the tip of a microelectrode. In many ways this technology circumvents the need for biochemical isolation and reconstitution.Maintenance of the Na + and K + concentrations in neurons requires the classical Na, + K + -ATPase that is found in all cell types. Recent experiments suggest that a novel form of this enzyme exists in neural tissues. This pump appears to be localized to anatomically and functionally distinct regions of many neurons. To restore the cytoplasmic Ca 2+ concentrations to original levels, the nerve terminal has an array of Ca 2+ removal systems including a Na + :Ca 2+ antiporter in the plasma membrane, a Ca 2+ porter in the mitochondrial inner membrane and several distinct ATP-dependent Ca 2+ uptake systems in the plasma membrane, smooth endoplasmic reticulum, and synaptic vesicles.The...

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“…An enhanced metabolism of these lipids was observed after receptor activation by transmitters, hormones and neuropeptides which utilize calcium ions as their second messenger (Abdel-Latif, 1983;Michell, 1979).…”

Section: Introductionmentioning

confidence: 99%

Immunochemical characterization of phosphatidylinositol 4-phosphate kinase from rat brain

Dongen¹,

Schrama²,

Oestreicher³

et al. 1986

Biochemical Journal

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Affinity-purified antibodies were used to identify a protein of molecular mass 45 kDa (45 kDa protein) in rat brain cytosol as phosphatidylinositol 4-phosphate (PtdIns4P) kinase. Antibodies were raised in rabbits by immunization with the purified 45 kDa protein. Anti-(45 kDa protein) immunoglobulins were isolated by affinity chromatography of the antiserum on a solid immunosorbent, which was prepared by coupling a soluble rat brain fraction, the DEAE-cellulose pool containing 10-15% 45 kDa protein, to CNBr-activated Sepharose 4B. The purified IgGs were specific for the 45 kDa protein as judged by immunoblot and by immunoprecipitation. The purified anti-(45 kDa protein) IgGs inhibited the enzyme activity of partially purified PtdIns4P kinase, whereas preimmune IgGs were ineffective. Immunoprecipitation of the 45 kDa protein from the partially purified enzyme preparation with the purified IgGs resulted in a concomitant decrease in the amount of 45 kDa protein and in PtdIns4P kinase activity. The amount of 45 kDa protein remaining in the supernatant and the activity of PtdIns4P kinase correlated with a coefficient of r = 0.87. The evidence presented lends further support for the notion that the catalytic activity of PtdIns4P kinase in rat brain cytosol resides in a 45 kDa protein.

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Inositol phospholipids in membrane function

Cited by 275 publications

References 25 publications

Suppression of phagocytic function and phospholipid metabolism in macrophages by phosphatidylinositol liposomes.

Suppression of phagocytic function and phospholipid metabolism in macrophages by phosphatidylinositol liposomes.

A Molecular Description of Nerve Terminal Function

Immunochemical characterization of phosphatidylinositol 4-phosphate kinase from rat brain

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