A functional coupling between CRMP1 and Nav1.7 for retrograde propagation of Semaphorin3A signaling

Yamane, Masayuki; Yamashita, Naoya; Hida, Tomonobu; Kamiya, Yoshinori; Nakamura, Fumio; Kolattukudy, Pappachan E.; Goshima, Yoshio

doi:10.1242/jcs.199737

Cited by 15 publications

(11 citation statements)

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“…CRMP1 and CRMP4 are sequentially and functionally close to CRMP2, and their expression pattern partially overlaps . Moreover, CRMP4 (Fig EV2) and CRMP1 are expressed in peripheral nerves suggesting that their elevation could rescue the reduced axon growth caused by acute CRMP2 deficiency. Increased expression of CRMP1 or CRMP4 could partially compensate for CRMP2 deficiency not only in Sema3A‐dependent axon guidance but also in pruning, as we did not detect significant defects in Sema3A‐dependent axon pruning in crmp2 −/− neurons in vivo or in vitro (Figs and EV3).…”

Section: Discussionmentioning

confidence: 95%

CRMP 2 mediates Sema3F‐dependent axon pruning and dendritic spine remodeling

et al. 2020

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Regulation of axon guidance and pruning of inappropriate synapses by class 3 semaphorins are key to the development of neural circuits. Collapsin response mediator protein 2 (CRMP2) has been shown to regulate axon guidance by mediating semaphorin 3A (Sema3A) signaling; however, nothing is known about its role in synapse pruning. Here, using newly generated crmp2−/− mice we demonstrate that CRMP2 has a moderate effect on Sema3A‐dependent axon guidance in vivo, and its deficiency leads to a mild defect in axon guidance in peripheral nerves and the corpus callosum. Surprisingly, crmp2−/− mice display prominent defects in stereotyped axon pruning in hippocampus and visual cortex and altered dendritic spine remodeling, which is consistent with impaired Sema3F signaling and with models of autism spectrum disorder (ASD). We demonstrate that CRMP2 mediates Sema3F signaling in primary neurons and that crmp2−/− mice display ASD‐related social behavior changes in the early postnatal period as well as in adults. Together, we demonstrate that CRMP2 mediates Sema3F‐dependent synapse pruning and its dysfunction shares histological and behavioral features of ASD.

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Section: Discussionmentioning

confidence: 95%

CRMP 2 mediates Sema3F‐dependent axon pruning and dendritic spine remodeling

et al. 2020

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“…CRMP2 trafficking of multiple ion channels could allow for dual targeting of calcium and sodium signaling to produce antinociception. Whether the other four members of the CRMP family couple to Na V 1.7 is unknown except for a report demonstrating that CRMP1 interacts with Na V 1.7 to mediate retrograde axonal signaling of the axon guidance molecule semaphorin 3A [106].…”

Section: (N) Collapsin Response Mediator Protein 2 (Crmp2)mentioning

confidence: 99%

Mining the Nav1.7 interactome: Opportunities for chronic pain therapeutics

Chew

Bellampalli

Dustrude

et al. 2019

Biochemical Pharmacology

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The peripherally expressed voltage-gated sodium Na V 1.7 (gene SCN9A) channel boosts small stimuli to initiate firing of pain-signaling dorsal root ganglia (DRG) neurons and facilitates neurotransmitter release at the first synapse within the spinal cord. Mutations in SCN9A produce distinct human pain syndromes. Widely acknowledged as a "gatekeeper" of pain, Na V 1.7 has been the focus of intense investigation but, to date, no Na V 1.7-selective drugs have reached the clinic. Elegant crystallographic studies have demonstrated the potential of designing highly potent and selective Na V 1.7 compounds but their therapeutic value remains untested. Transcriptional silencing of Na V 1.7 by a naturally expressed antisense transcript has been reported in rodents and humans but whether this represents a viable opportunity for designing Na V 1.7 therapeutics is currently unknown. The demonstration that loss of Na V 1.7 function is associated with upregulation of endogenous opioids and potentiation of mu-and delta-opioid receptor activities, suggests that targeting only Na V 1.7 may be insufficient for analgesia. However, the link between opioid-dependent analgesic mechanisms and function of sodium channels and intracellular sodium-dependent signaling remains controversial and disputed. Thus, additional new targetsregulators, modulators-are needed. In this context, we mine the literature for the known interactome of Na V 1.7 with a focus on protein interactors that affect the channel's trafficking or

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“…6 Semaphorin-3A (Sema3A), a neuronal secreted chemorepulsive guidance cue that binds to the PlexinA1 and NRP-1 co-receptor, induces neuronal growth cone collapse in an autocrine manner and modulates RhoA/ ROCK pathway in PC12 cells and rat Parkinson disease model. [7][8][9][10] Thus, sema3A can regulate neuronal axon growth via both intrinsic and extrinsic manner. RhoA/ROCK pathway is recognized as a negative modulatory pathway that inhibits neuronal axon growth.…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, aiming to enhance the neuronal intrinsic regenerative capability after injury is of great importance 6 . Semaphorin‐3A (Sema3A), a neuronal secreted chemorepulsive guidance cue that binds to the PlexinA1 and NRP‐1 co‐receptor, induces neuronal growth cone collapse in an autocrine manner and modulates RhoA/ROCK pathway in PC12 cells and rat Parkinson disease model 7‐10 . Thus, sema3A can regulate neuronal axon growth via both intrinsic and extrinsic manner.…”

Section: Introductionmentioning

confidence: 99%