Neurotransmitter release regulated by nitric oxide in PC-12 cells and brain synaptosomes

Hirsch, David; Steiner, Joseph P.; Dawson, Ted M.; Mammen, Andrew L.; Hayek, Emil; Snyder, Solomon H.

doi:10.1016/0960-9822(93)90022-g

Cited by 107 publications

(52 citation statements)

References 33 publications

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“…Like synapsins, NO has been localized in presynaptic terminals to the presynaptic cytoskeleton, including actin and microtubules (6), as well as synaptic vesicles (6). NO has multiple functions within neurons, such as influencing release of neurotransmitters from synaptic vesicles (2,33,34), through a mechanism that most likely involves S-nitrosylation (35). Additionally, nNOS Ϫ/Ϫ mice display defects in dendritic arborization (5), which are similar to dendritic defects found in synapsin I knockout mice (26).…”

Section: Discussionmentioning

confidence: 88%

Neuronal nitric-oxide synthase localization mediated by a ternary complex with synapsin and CAPON

Jaffrey

Benfenati

Snowman

et al. 2002

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

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106

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The specificity of the reactions of nitric oxide (NO) with its neuronal targets is determined in part by the precise localizations of neuronal NO synthase (nNOS) within the cell. The targeting of nNOS is mediated by adapter proteins that interact with its PDZ domain. Here, we show that the nNOS adapter protein, CAPON, interacts with synapsins I, II, and III through an N-terminal phosphotyrosinebinding domain interaction, which leads to a ternary complex comprising nNOS, CAPON, and synapsin I. The significance of this ternary complex is demonstrated by changes in subcellular localization of nNOS in mice harboring genomic deletions of both synapsin I and synapsin II. These results suggest a mechanism for specific actions of NO at presynaptic sites.

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Section: Discussionmentioning

confidence: 88%

Neuronal nitric-oxide synthase localization mediated by a ternary complex with synapsin and CAPON

Jaffrey

Benfenati

Snowman

et al. 2002

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

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106

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“…In rats, NGF enhances expression of nNOS by cholinergic neurons of the basal forebrain (12). NGF treatment of PC12 cells induces expression of all three isoforms of NOS (2,3), and inhibitors of NOS block NGFinduced cessation of proliferation and neurite extension for PC12 cells (3). Hence, NO acts as a regulator of cell proliferation which, in turn, influences process outgrowth.…”

mentioning

confidence: 99%

“…Nerve growth factor (NGF) 1 induces both cell cycle arrest and differentiation for PC12 pheochromocytoma cells (1). These effects are associated with induction of nitric oxide synthase (NOS) (2,3), the p53 tumor suppressor (4), and the p21 WAF1 cyclin-dependent kinase inhibitor (5-7). However, the relationship among these signaling events, arrest, and differentiation is poorly understood.…”

mentioning

confidence: 99%

A Novel, Nerve Growth Factor-activated Pathway Involving Nitric Oxide, p53, and p21WAF1 Regulates Neuronal Differentiation of PC12 Cells

Poluha

Schonhoff

Harrington

et al. 1997

Journal of Biological Chemistry

141

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“…This disparity may partly relate to cell-specific regulatory events, particularly in regard to studies using nerve terminals (synaptosomes), cultured neuronal cells, and brain slices. Effects on neurotransmitter release from nerve terminals are more clearly related to potentially direct actions of cGMP on the molecular machinery of vesicle traffic (Hirsch et al, 1993;Montague et al, 1994;Kamisaki et al, 1995) or neurotransmitter uptake mechanisms (Pogun et al, 1994). Effects in cultured neurons may be attributed to effects within single cells or local interactions between related cells (Hirsch et al, 1993;Meriney eta!., 1994).…”

Section: Modulation Of Neurotransmitter Releasementioning

confidence: 99%

“…Effects on neurotransmitter release from nerve terminals are more clearly related to potentially direct actions of cGMP on the molecular machinery of vesicle traffic (Hirsch et al, 1993;Montague et al, 1994;Kamisaki et al, 1995) or neurotransmitter uptake mechanisms (Pogun et al, 1994). Effects in cultured neurons may be attributed to effects within single cells or local interactions between related cells (Hirsch et al, 1993;Meriney eta!., 1994). However, effects in brain slices may relate to complex interactions between nerve cells and glia and cannot easily be attributed to the direct action of cGMP in nerve endings (Lonart et al, 1993;Zhuo et al, 1994).…”

Section: Modulation Of Neurotransmitter Releasementioning

confidence: 99%

Cyclic GMP‐Dependent Protein Kinase and Cellular Signaling in the Nervous System

Wang

Robinson

1997

Journal of Neurochemistry

264

128

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Nitric oxide (NO) and natriuretic peptide hormones play key roles in a surprising number of neuronal functions, including learning and memory. Most data suggest that they exert converging actions by elevation of intracellular cyclic GMP (cGMP) levels through activation of soluble and particulate guanylyl cyclases. However, cGMP is only the starting point for multiple signaling cascades, which are now beginning to be defined. A primary action of elevated cGMP levels is the stimulation of cGMP-dependent protein kinase (PKG), the major intracellular receptor protein for cGMP, which phosphorylates substrate proteins to exert its actions. It has become increasingly clear that PKG mediates some of the neuronal effects of cGMP, but how is not yet clear. One clear illustration of this pathway has been reported in striatonigral nerve terminals, where NO mediates phosphorylation of the protein phosphatase regulator dopamine-and cyclic AM P-regulated phosphoprotein having a molecular mass of 32,000 (DARPP-32) by PKG. There are remarkably few PKG substrates in brain whose identities are known. A survey of these proteins and those known from other tissues that might also be found in the nervous system reveals the key molecular sites where cGMP and PKG signaling is likely to be regulating neural function. These potential substrates are critically placed to have profound effects on the protein phosphorylation network through regulation of protein phosphatases, intracellular calcium levels, and the function of many ion channels and neurotransmitter receptors. The brain also contains a rich diversity of specific PKG substrates whose identities are not yet known. Their future identification will provide exciting new leads that will permit better understanding of the role of PKG signaling in both basic and higher orders of brain function. Key Words: Protein phosphorylation-Cyclic GMP-Cyclic GMP-dependent protein kinase-BrainNeuron-Neurotransmitter release. J. Neurochem. 68, 443-456 (1997).The widespread biological importance of cyclic GMP (cGMP) signaling through cGMP-dependent protein kinase (PKG) has been slow to be appreciated. Despite an exciting flourish of activity in the late I 960s and early 1970s when both cGMP and PKG were discovered, research largely languished for many years and was focused in only a small number of laboratories. This was probably due to the difficulty in determining how this signaling system was activated, what biological processes it regulated, and what substrates of PKG might mediate its actions. PKG' s role in smooth muscle relaxation has been the most significant area of productive research. It was not until more recent years that it was discovered that two pathways lead to cGMP signaling, via natriuretic peptides such as atrial natriuretic peptide (ANP) and soluble gases such as nitric oxide (NO) and carbon monoxide, which elevate intracellular cGMP levels through activation of particulate (GC-P) and soluble (GC-S) guanylyl cyclases (Fig. 1). In the last few years there has been an expl...

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Neurotransmitter release regulated by nitric oxide in PC-12 cells and brain synaptosomes

Cited by 107 publications

References 33 publications

Neuronal nitric-oxide synthase localization mediated by a ternary complex with synapsin and CAPON

Neuronal nitric-oxide synthase localization mediated by a ternary complex with synapsin and CAPON

A Novel, Nerve Growth Factor-activated Pathway Involving Nitric Oxide, p53, and p21WAF1 Regulates Neuronal Differentiation of PC12 Cells

Cyclic GMP‐Dependent Protein Kinase and Cellular Signaling in the Nervous System

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