The Neuronal Growth-Associated Protein GAP-43 Interacts with Rabaptin-5 and Participates in Endocytosis

Neve, Rachael L.; Coopersmith, Robert; McPhie, Donna L.; Santeufemio, C.; Pratt, Kara G.; Murphy, Christian; Lynn, Stephanie D.

doi:10.1523/jneurosci.18-19-07757.1998

Cited by 83 publications

(64 citation statements)

References 46 publications

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“…This GTPase mediates membrane fusion in endocytosis. Through this interaction GAP-43 appears to modulate endocytosis and synaptic vesicle recycling [67]. GAP-43 was shown to colocalize with rabaptin-5 in the synaptosome-enriched fraction obtained from primary cultures of rat cortical neurons.…”

Section: Gap-43 G Proteins Small Gtpases and Filopodiamentioning

confidence: 96%

“…For example, the formation of lamellipodia is promoted by Rac1, while the formation of filopodia is promoted by cdc42 [37]. Some initial findings regarding GAP-43 and small GTPases were obtained when proteins were sought which interact with GAP-43 in the presence of calcium [67]. It was shown that GAP-43 interacts with rabaptin-5, which is an effector of the GTPase Rab5.…”

Section: Gap-43 G Proteins Small Gtpases and Filopodiamentioning

confidence: 99%

“…GAP-43 was shown to colocalize with rabaptin-5 in the synaptosome-enriched fraction obtained from primary cultures of rat cortical neurons. Overexpression of GAP-43 in neurons was found to decrease the size of Rab5-containing endosomes, and this effect was altered by mutations affecting the ability of GAP-43 to bind calmodulin [67].…”

Section: Gap-43 G Proteins Small Gtpases and Filopodiamentioning

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 G Proteins Small Gtpases and Filopodiamentioning

confidence: 96%

Section: Gap-43 G Proteins Small Gtpases and Filopodiamentioning

confidence: 99%

Section: Gap-43 G Proteins Small Gtpases and Filopodiamentioning

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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“…Replication-defective HSV vectors expressing sGFPGAP cDNA or β-gal in the plasmid pHSVPrpUC were prepared as previously described (2,5). The titer of the helper virus component of each stock was 1-1.2 × 10 6 plaqueforming units (pfu)/mL on 2-2 cells.…”

Section: Generation Of Recombinant Hsv Vectorsmentioning

confidence: 99%

“…Increasingly, infection with recombinant viral vectors is being used for the delivery of genes into primary neuronal cells (1,3,(5)(6)(7). Often, particularly in the study of in situ protein-protein interactions, an experimental protocol depends on the co-expression of two genes in the same cell.…”

Section: Introductionmentioning

confidence: 99%

Expression of Multiple Proteins within Single Primary Cortical Neurons Using a Replication Deficient HSV Vector

Coopersmith

Neve

1999

BioTechniques

Self Cite

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The study of protein-protein interactions in the nervous system has become dependent on the ability to express foreign proteins (or to overexpress endogenous proteins) within neurons. Often, multiple genes need to be overexpressed in the same cell. To investigate the simultaneous co-expression of more than one virally introduced gene in primary cortical neurons, we infected cultures with two different herpes simplex virus (HSV) vectors and analyzed the proportion of singly and doubly infected cells. The vast majority of neurons expressed both gene products, with a smaller number expressing one or the other protein alone. Increasing the quantity of virus caused an increase in the proportion of doubly labeled cells at the expense of singly labeled cells, which is consistent with a model in which infection with one viral vector is independent of infection with the other. We conclude that co-infection with HSV vectors is an efficient way to obtain expression of multiple gene products within individual primary culture neurons. INTRODUCTIONIncreasingly, infection with recombinant viral vectors is being used for the delivery of genes into primary neuronal cells (1,3,(5)(6)(7). Often, particularly in the study of in situ protein-protein interactions, an experimental protocol depends on the co-expression of two genes in the same cell. While vectors have been described that express multiple gene products either using separate expression cassettes (4) or as multiple genes driven by the same promoter using an internal ribosome entry site (8), these methods do not allow the combinatorial flexibility afforded by multiple infection with separate vectors. An implicit assumption in co-infection experiments is that the expression of each virally introduced gene is independent of the other; the proportion of singly and doubly infected cells would then be expected to fit a binomial distribution. Alternatively, successful infection of a cell with one viral vector might diminish or even preclude infection with the second vector.To distinguish between these possibilities, we infected primary neuronal cultures with replication-defective herpes simplex virus (HSV) vectors expressing either a fusion protein of the neuronal growth-associated protein GAP-43 with sGFP (HSVGFPGAP) and/or Escherichia coli β-galactosidase (β-gal) (HSVlac). Counts of singly and doubly infected cells suggest that successful infection by each of the two vectors is an independent event, yielding a high proportion of double-infected neurons. MATERIALS AND METHODS Generation of Recombinant HSV VectorsReplication-defective HSV vectors expressing sGFPGAP cDNA or β-gal in the plasmid pHSVPrpUC were prepared as previously described (2,5). The titer of the helper virus component of each stock was 1-1.2 × 10 6 plaqueforming units (pfu)/mL on 2-2 cells. The titer of the recombinant virus component of each stock, as assayed by expression of the exogenous gene in PC12 cells, was consistently 3 × 10 7 infectious units (iu)/mL. Primary Neuronal CulturesPrimary cortica...

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Transdifferentiation of chondrocytes into neuron‐like cells induced by neuronal lineage specifying growth factors

Greene

Green²,

Sherwin³

2014

Cell Biology International

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We previously reported that neural-crest-derived stromal cells from adult human and rat corneas can differentiate into neuron-like cells when treated with neuronal lineage specifying growth factors. However, it remains unclear whether this level of cell plasticity is unique to the corneal stromal cell population present in the eye. In this study, non-neural-crest-derived chondrocytes from the xiphosternum of adult rats were subjected to the same differentiation protocol. Cells of the adult rat xiphosternum can also differentiate into neuron-like cells when treated with neurogenic differentiation specifying growth factors. After 1 week in neurogenic differentiation culture conditions, the chondrocytes changed from a round to a stellate morphology and started to express neuron-specific protein neurofilament-200 (NF-200), microtubule associated protein-2 (Map-2), and β-III tubulin. Lineage-specifying growth factors can affect changes in morphology and protein expression of adult cells in culture, findings that challenge the notion of a restricted differentiation potential of adult cell populations and questions the stability of the differentiated state of cells.

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The Neuronal Growth-Associated Protein GAP-43 Interacts with Rabaptin-5 and Participates in Endocytosis

Cited by 83 publications

References 46 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

Expression of Multiple Proteins within Single Primary Cortical Neurons Using a Replication Deficient HSV Vector

Transdifferentiation of chondrocytes into neuron‐like cells induced by neuronal lineage specifying growth factors

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