Growth-associated Protein-43 (GAP-43) Facilitates Peptide Hormone Secretion in Mouse Anterior Pituitary AtT-20 Cells

Gamby, Chantal; Waage, Martha C.; Allen, Richard B.; Baizer, Lawrence

doi:10.1074/jbc.271.17.10023

Cited by 25 publications

(29 citation statements)

References 80 publications

(60 reference statements)

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“…The cells were transfected with GAP-43 cDNA. Potassium-stimulated release of -endorphin was greatly enhanced in those cells expressing GAP-43, without a significant change in calcium influx, while corticotropin-releasing factor-evoked hormone secretion was not affected [32]. The transfected cells also showed extended processes when plated on laminin-coated substrates [32].…”

Section: Gap-43 Neurotransmitters and Pharma-cological Agentsmentioning

confidence: 91%

“…Potassium-stimulated release of -endorphin was greatly enhanced in those cells expressing GAP-43, without a significant change in calcium influx, while corticotropin-releasing factor-evoked hormone secretion was not affected [32]. The transfected cells also showed extended processes when plated on laminin-coated substrates [32]. Angiotensin II, when binding to the angiotensin type 1 receptor, increased GAP-43 expression and neurite extension [101].…”

Section: Gap-43 Neurotransmitters and Pharma-cological Agentsmentioning

confidence: 99%

“…As indicated above, GAP-43 may assist in the release of dopamine from amacrine cells in the retina [46]. GAP-43 promotes peptide hormone secretion in mouse anterior pituitary AtT-20 cells [32]. The cells were transfected with GAP-43 cDNA.…”

Section: Gap-43 Neurotransmitters and Pharma-cological Agentsmentioning

confidence: 99%

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Molecular Mechanisms, Biological Actions, and Neuropharmacology of the Growth-Associated Protein GAP-43

Denny

2006

202

166

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GAP-43 is an intracellular growth-associated protein that appears to assist neuronal pathfinding and branching during development and regeneration, and may contribute to presynaptic membrane changes in the adult, leading to the phenomena of neurotransmitter release, endocytosis and synaptic vesicle recycling, long-term potentiation, spatial memory formation, and learning. GAP-43 becomes bound via palmitoylation and the presence of three basic residues to membranes of the early secretory pathway. It is then sorted onto vesicles at the late secretory pathway for fast axonal transport to the growth cone or presynaptic plasma membrane. The palmitate chains do not serve as permanent membrane anchors for GAP-43, because at steady-state most of the GAP-43 in a cell is membrane-bound but is not palmitoylated. Filopodial extension and branching take place when GAP-43 is phosphorylated at Ser-41 by protein kinase C, and this occurs following neurotrophin binding and the activation of numerous small GTPases. GAP-43 has been proposed to cluster the acidic phospholipid phosphatidylinositol 4,5-bisphosphate in plasma membrane rafts. Following GAP-43 phosphorylation, this phospholipid is released to promote local actin filament-membrane attachment. The phosphorylation also releases GAP-43 from calmodulin. The released GAP-43 may then act as a lateral stabilizer of actin filaments. N-terminal fragments of GAP-43, containing 10-20 amino acids, will activate heterotrimeric G proteins, direct GAP-43 to the membrane and lipid rafts, and cause the formation of filopodia, possibly by causing a change in membrane tension. This review will focus on new information regarding GAP-43, including its binding to membranes and its incorporation into lipid rafts, its mechanism of action, and how it affects and is affected by extracellular agents.

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Section: Gap-43 Neurotransmitters and Pharma-cological Agentsmentioning

confidence: 91%

Section: Gap-43 Neurotransmitters and Pharma-cological Agentsmentioning

confidence: 99%

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Molecular Mechanisms, Biological Actions, and Neuropharmacology of the Growth-Associated Protein GAP-43

Denny

2006

202

166

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“…We reported recently that forced expression of neuromodulin in mouse anterior pituitary AtT-20 cells enhanced K ϩ -evoked hormone secretion and induced changes in cellular morphology (59). These results suggested that AtT-20 cells would be a useful experimental system to explore the molecular mechanism(s) of neuromodulin action.…”

mentioning

confidence: 93%

“…The original AtT-20 cells were transfected using the LipofectAMINE reagent, according to the manufacturer's instructions as described previously (59). Permanent transfected cell lines were selected in medium containing 400 g/ml G418.…”

mentioning

confidence: 99%

Analysis of the Role of Calmodulin Binding and Sequestration in Neuromodulin (GAP-43) Function

Gamby

Waage

Allen

et al. 1996

Journal of Biological Chemistry

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We demonstrated previously that forced expression of the neuronal phosphoprotein neuromodulin (also known as GAP-43, F1, B-50, and p57) in mouse anterior pituitary AtT-20 cells enhances depolarization-mediated secretion and alters cellular morphology. Here we analyze the role of calmodulin binding by neuromodulin in these responses. In cells expressing wild-type neuromodulin, a complex with calmodulin that is sensitive to intracellular calcium and phosphorylation is localized to the plasma membrane. Transfection of several mutant forms of neuromodulin shows that the effects of this protein on secretion are dependent on both calmodulin binding and association with the plasma membrane. In contrast, the morphological changes depend only on membrane association. Thus, the multitude of effects of neuromodulin noted in previous studies may result from divergent properties of this protein.The neuronal growth-associated protein neuromodulin (also designated GAP-43, B-50, and F1) is a membrane-bound phosphoprotein expressed at a high level during neuronal development and regeneration (reviewed in Refs. 1 and 2). Neuromodulin is a rapidly transported axonal protein (3-10) that is concentrated in the growth cone of elongating axons (8,(11)(12)(13)(14)(15)(16)(17). Additionally, overexpression of neuromodulin in the nervous system of transgenic mice causes spontaneous nerve sprouting at the neuromuscular junction and potentiates lesion-induced nerve sprouting and terminal arborization during re-innervation (18). Taken together, these results suggest that neuromodulin plays an important role in axon elongation. Further support for this notion has been derived from studies of several cell culture model systems (19 -28).However, a line of PC12 cells in which neuromodulin expression is nearly undetectable is nevertheless capable of robust neurite elongation in response to nerve growth factor (29). Additionally, cultured neurons derived from mice in which the neuromodulin gene has been disrupted by gene targeting extend axons to the same extent as cells that express this protein.Further analysis of the neuromodulin (Ϫ) embryos revealed that retinal axons appear incapable of crossing the midline decision point in the optic chiasm, implying that their growth cones fail to respond to environmental guidance cues (30).These results suggest that neuromodulin is perhaps not essential for axon elongation, but rather might function as a mediator of signal transduction pathways in the growth cone that serve to modulate the rate, extent, and trajectory of axonal growth.In the adult nervous system, neuromodulin expression persists in pre-synaptic terminals in those regions where the synaptic modifications associated with learning and memory are thought to occur (31-36). Additionally, the correlation of PKC 1 -mediated neuromodulin phosphorylation with long term potentiation of synaptic transmission in the hippocampus (37-40) and neurotransmitter release in vitro (41) suggest a role for neuromodulin in neuronal plasticity, possibly via modul...

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The Motility-Associated Proteins GAP-43, MARCKS, and CAP-23 Share Unique Targeting and Surface Activity-Inducing Properties

Wiederkehr

Staple²,

Caroni

1997

Experimental Cell Research

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Growth-associated Protein-43 (GAP-43) Facilitates Peptide Hormone Secretion in Mouse Anterior Pituitary AtT-20 Cells

Cited by 25 publications

References 80 publications

Molecular Mechanisms, Biological Actions, and Neuropharmacology of the Growth-Associated Protein GAP-43

Molecular Mechanisms, Biological Actions, and Neuropharmacology of the Growth-Associated Protein GAP-43

Analysis of the Role of Calmodulin Binding and Sequestration in Neuromodulin (GAP-43) Function

The Motility-Associated Proteins GAP-43, MARCKS, and CAP-23 Share Unique Targeting and Surface Activity-Inducing Properties

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