GAP-43 in synaptic plasticity: molecular perspectives

Holahan, Matthew R.

doi:10.2147/rrbc.s73846

Cited by 25 publications

(19 citation statements)

References 115 publications

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“…An important consideration in determining that GAP-43 is a supporting factor in axonal outgrowth and function is through the examination of protein interactions (see Holahan, 2015 for summary diagrams). When GAP-43 is phosphorylated by PKC following rises in intracellular Ca 2+ , it interacts with other proteins to facilitate axonal elongation and vesicular cycling.…”

Section: Gap-43 Proteinmentioning

confidence: 99%

A Shift from a Pivotal to Supporting Role for the Growth-Associated Protein (GAP-43) in the Coordination of Axonal Structural and Functional Plasticity

Holahan

2017

Front. Cell. Neurosci.

132

100

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In a number of animal species, the growth-associated protein (GAP), GAP-43 (aka: F1, neuromodulin, B-50, G50, pp46), has been implicated in the regulation of presynaptic vesicular function and axonal growth and plasticity via its own biochemical properties and interactions with a number of other presynaptic proteins. Changes in the expression of GAP-43 mRNA or distribution of the protein coincide with axonal outgrowth as a consequence of neuronal damage and presynaptic rearrangement that would occur following instances of elevated patterned neural activity including memory formation and development. While functional enhancement in GAP-43 mRNA and/or protein activity has historically been hypothesized as a central mediator of axonal neuroplastic and regenerative responses in the central nervous system, it does not appear to be the crucial substrate sufficient for driving these responses. This review explores the historical discovery of GAP-43 (and associated monikers), its transcriptional, post-transcriptional and post-translational regulation and current understanding of protein interactions and regulation with respect to its role in axonal function. While GAP-43 itself appears to have moved from a pivotal to a supporting factor, there is no doubt that investigations into its functions have provided a clearer understanding of the biochemical underpinnings of axonal plasticity.

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Section: Gap-43 Proteinmentioning

confidence: 99%

A Shift from a Pivotal to Supporting Role for the Growth-Associated Protein (GAP-43) in the Coordination of Axonal Structural and Functional Plasticity

Holahan

2017

Front. Cell. Neurosci.

132

100

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“…6, A and B). PKC, GAP-43, and CaM all play a role in the modification of the actin cytoskeleton via different actin-remodeling proteins (28,36,37). Therefore, we made use of phalloidin to mark filamentous actin (F-actin) in dissociated cortical neurons.…”

Section: Il-4 Effects On Neurons Are Due To Fast Direct Neuron-specifmentioning

confidence: 99%

Fast direct neuronal signaling via the IL-4 receptor as therapeutic target in neuroinflammation

et al. 2018

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Ongoing axonal degeneration is thought to underlie disability in chronic neuroinflammation, such as multiple sclerosis (MS), especially during its progressive phase. Upon inflammatory attack, axons undergo pathological swelling, which can be reversible. Because we had evidence for beneficial effects of T helper 2 lymphocytes in experimental neurotrauma and discovered interleukin-4 receptor (IL-4R) expressed on axons in MS lesions, we aimed at unraveling the effects of IL-4 on neuroinflammatory axon injury. We demonstrate that intrathecal IL-4 treatment during the chronic phase of several experimental autoimmune encephalomyelitis models reversed disease progression without affecting inflammation. Amelioration of disability was abrogated upon neuronal deletion of IL-4R. We discovered direct neuronal signaling via the IRS1-PI3K-PKC pathway underlying cytoskeletal remodeling and axonal repair. Nasal IL-4 application, suitable for clinical translation, was equally effective in improving clinical outcome. Targeting neuronal IL-4 signaling may offer new therapeutic strategies to halt disability progression in MS and possibly also neurodegenerative conditions.

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“…As growth-associated protein 43 (Gap-43) is known to be expressed in outgrowing axons, regrowth of the injured axons was visualized within horizontal visual system sections of Tg(Gap-43:eGFP) fish ( Fig. 2A) (Holohan, 2015).…”

Section: Axonal Outgrowth Is Decelerated In Aged Fishmentioning

confidence: 99%

Successful optic nerve regeneration in the senescent zebrafish despite age-related decline of cell intrinsic and extrinsic response processes

houcke

Bollaerts

Geeraerts

et al. 2017

Neurobiology of Aging

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Dysfunction of the central nervous system (CNS) in neurodegenerative diseases or after brain lesions seriously affects life quality of a growing number of elderly, since the adult CNS lacks the capacity to replace or repair damaged neurons. Despite intensive research efforts, full functional recovery after CNS disease and/or injury remains challenging, especially in an aging environment. As such, there is a rising need for an aging model in which the impact of aging on successful regeneration can be studied. Here, we introduce the senescent zebrafish retinotectal system as a valuable model to elucidate the cellular and molecular processes underlying age-related decline in axonal regeneration capacities. We found both intrinsic and extrinsic response processes to be altered in aged fish. Indeed, expression levels of growth-associated genes are reduced in naive and crushed retinas, and the injury-associated increase in innate immune cell density appears delayed, suggesting retinal inflammaging in old fish. Strikingly, however, despite a clear deceleration in regeneration onset and early axon outgrowth leading to an overall slowing of optic nerve regeneration, reinnervation of the optic tectum and recovery of visual function occurs successfully in the aged zebrafish retinotectal system.

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GAP-43 in synaptic plasticity: molecular perspectives

Cited by 25 publications

References 115 publications

A Shift from a Pivotal to Supporting Role for the Growth-Associated Protein (GAP-43) in the Coordination of Axonal Structural and Functional Plasticity

A Shift from a Pivotal to Supporting Role for the Growth-Associated Protein (GAP-43) in the Coordination of Axonal Structural and Functional Plasticity

Fast direct neuronal signaling via the IL-4 receptor as therapeutic target in neuroinflammation

Successful optic nerve regeneration in the senescent zebrafish despite age-related decline of cell intrinsic and extrinsic response processes

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