Interactions between Plexin-A2, Plexin-A4, and Semaphorin 6A Control Lamina-Restricted Projection of Hippocampal Mossy Fibers

Suto, Fumikazu; Tsuboi, Miu; Kamiya, Haruyuki; Mizuno, H.; Kiyama, Yuji; Komai, Shoji; Shimizu, Masayuki; Sanbo, Makoto; Yagi, Takeshi; Hiromi, Yasushi; Chédotal, Alain; Mitchell, Kevin J.; Manabe, Toshiya; Fujisawa, Hajime

doi:10.1016/j.neuron.2007.01.028

Cited by 182 publications

(254 citation statements)

References 38 publications

(53 reference statements)

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“…Containing the entire region of PlexA4 ectodomain (Fig. 7a), the PlexA4-DN can be recognized by the anti-PlexA4 antibody 39 . To avoid this cross-reaction, we first employed mutant forms of PlexA1, another PlexA family molecule: PlexA1-DN and IPT domain of PlexA1 (PlexA1-IPT).…”

Section: Resultsmentioning

confidence: 99%

Plexin-A4-dependent retrograde semaphorin 3A signalling regulates the dendritic localization of GluA2-containing AMPA receptors

et al. 2014

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The dendritic targeting of neurotransmitter receptors is vital for dendritic development and function. However, how such localization is established remains unclear. Here we show that semaphorin 3A (Sema3A) signalling at the axonal growth cone is propagated towards the cell body by retrograde axonal transport and drives AMPA receptor GluA2 to the distal dendrites, which regulates dendritic development. Sema3A enhances glutamate receptor interacting protein 1-dependent localization of GluA2 in dendrites, which is blocked by knockdown of cytoplasmic dynein heavy chain. PlexinA (PlexA), a receptor component for Sema3A, interacts with GluA2 at the immunoglobulin-like Plexin-transcription-factor domain (PlexA-IPT) in somatodendritic regions. Overexpression of PlexA-IPT suppresses dendritic localization of GluA2 and induces aproximal bifurcation phenotype in the apical dendrites of CA1 hippocampal neurons. Thus, we propose a control mechanism by which retrograde Sema3A signalling regulates the glutamate receptor localization through trafficking of cis-interacting PlexA with GluA2 along dendrites.

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Section: Resultsmentioning

confidence: 99%

Plexin-A4-dependent retrograde semaphorin 3A signalling regulates the dendritic localization of GluA2-containing AMPA receptors

et al. 2014

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“…The DRG neurons were incubated with anti-PlexA4 antibody (1:500-1:2500 dilution) (Suto et al, 2007); anti-TrkA rabbit polyclonal antibodies (1:1000 dilution; 06-574, Millipore); anti-CRMP1 (1:400) antibody (2E7G) and anti-CRMP2 antibody (9F) (1:400) (Wako Pure Chemical) (Makihara et al, 2016); or anti-Na v 1.7 antibody (1:1000 dilution; ASC-008, Alomone Labs) diluted in Can Get Signal (Toyobo, Osaka, Japan) at 4°C overnight, and then incubated at room temperature for 1 h with Cy3-(Jackson) or Alexa-Fluor-594 (Life Technologies)-conjugated secondary antibodies diluted with TBS containing 0.05% Tween 20. The fluorescence microscopy images were generated using a laser confocal microscope (LSM510) with a water-immersed objective set at 40× (C-Apochromat) equipped with an Axioplan 2 imaging microscope (Zeiss, Oberkochen, Germany).…”

Section: Immunocytochemistry and Microscopymentioning

confidence: 99%

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

Yamane

Yamashita

Hida

et al. 2017

Journal of Cell Science

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Semaphorin3A (Sema3A) is a secreted type of axon guidance molecules that regulates axon wiring through neuropilin-1 (NRP1) and PlexinAs (PlexAs) receptor complex. Sema3A regulates the dendritic branching through a tetrodotoxin (TTX)-sensitive retrograde axonal transport of PlexAs and Tropomyosin-related kinase A (TrkA) complex. We here demonstrate that Nav1.7, a TTX-sensitive Na+ channel, by coupling with collapsin response mediator protein 1 (CRMP1), mediates the Sema3A-induced retrograde transport. In mouse dorsal root ganglion (DRG) neurons, Sema3A increased co-localization of PlexA4 and TrkA in the growth cones and axons. TTX treatment and RNAi knockdown of Nav1.7, sustained Sema3A-induced co-localized signals of PlexA4 and TrkA in growth cones, and suppressed the subsequent localization of PlexA4 and TrkA in distal axons. A similar localization phenotype was observed in crmp1−/− DRG neurons. Sema3A induced co-localization of CRMP1 and Nav1.7 in the growth cones. The half maximal voltage was increased in crmp1−/− neurons when compared to wild-type. In HEK293 cells, introduction of CRMP1 lowered the threshold of the coexpressed Nav1.7. These results suggest that Nav1.7 mediates through coupling with CRMP1 the axonal retrograde signaling of Sema3A.

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“…In other systems, elevated cAMP levels have been associated with aberrant axonal targeting through CREB-mediated transcriptional regulation of key pathfinding molecules, including those molecules belonging to neuropilin/plexin/semaphorin signaling complexes (29). The axonal lamination phenotype observed in Disc1 Tm1Kara mutant mice and the fact that neuropilins and plexins have been extensively implicated in MF targeting, laminar-restricted positioning (30,31), and more recently, GC dendritic outgrowth (32) prompted us to assess their levels in the DG of Disc1 Tm1Kara mutant mice. qRT-PCR analysis on RNA from isolated DG (Fig.…”

Section: Disc1 Tm1karamentioning

confidence: 99%

Altered axonal targeting and short-term plasticity in the hippocampus of Disc1 mutant mice

Kvajo

McKellar

et al. 2011

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

106

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Carefully designed animal models of genetic risk factors are likely to aid our understanding of the pathogenesis of schizophrenia. Here, we study a mouse strain with a truncating lesion in the endogenous Disc1 ortholog designed to model the effects of a schizophreniapredisposing mutation and offer a detailed account of the consequences that this mutation has on the development and function of a hippocampal circuit. We uncover widespread and cumulative cytoarchitectural alterations in the dentate gyrus during neonatal and adult neurogenesis, which include errors in axonal targeting and are accompanied by changes in short-term plasticity at the mossy fiber/CA3 circuit. We also provide evidence that cAMP levels are elevated as a result of the Disc1 mutation, leading to altered axonal targeting and dendritic growth. The identified structural alterations are, for the most part, not consistent with the growthpromoting and premature maturation effects inferred from previous RNAi-based Disc1 knockdown. Our results provide support to the notion that modest disturbances of neuronal connectivity and accompanying deficits in short-term synaptic dynamics is a general feature of schizophrenia-predisposing mutations. psychiatric disease | rare mutation | mouse model T he schizophrenia (SCHZ) susceptibility gene DISC1 was identified through a balanced chromosomal translocation (1;11)(q42.1;q14.3) segregating with SCHZ and mood disorders in a large Scottish pedigree. This is the only confirmed disease risk allele within the DISC1 locus. The biology of DISC1 is being interrogated with a variety of approaches, such as acute RNAimediated gene knockdown (1-4), overexpression of truncated forms of the human DISC1 (5, 6), and chemical mutagenesis (7). Although they provide information about potential pathways related to DISC1, these approaches are not meant to recapitulate the integrated effects of the pathogenic translocation, and the relevance of these findings to SCHZ pathogenesis remains uncertain.We used a disease-focused knockin approach to introduce a truncating lesion in the endogenous murine Disc1 ortholog designed to model the effects of the (1;11) translocation (Mouse Genome Informatics nomenclature Disc1 Tm1Kara ) (8, 9). Although the divergence in the human and mouse Disc1 gene does not allow an exact replication of the human translocation, this mouse model approximates very closely the Scottish mutation. One advantage of our approach is that it retains endogenous levels as well as spatial and temporal patterns of Disc1 expression, and it preserves short N-terminal isoforms that are presumably unaffected by the Scottish translocation and seem to be expressed at relatively higher levels in the hippocampus (HPC) of patients with SCHZ (10). A comprehensive behavioral analysis has shown that Disc1 Tm1Kara mice display a unique profile of cognitive impairments, including specific and robust deficiencies in working memory (WM) tests (8, 9), which may relate to similar cognitive deficits prominent in psychotic disorders.DISC1 is...

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Interactions between Plexin-A2, Plexin-A4, and Semaphorin 6A Control Lamina-Restricted Projection of Hippocampal Mossy Fibers

Cited by 182 publications

References 38 publications

Plexin-A4-dependent retrograde semaphorin 3A signalling regulates the dendritic localization of GluA2-containing AMPA receptors

Plexin-A4-dependent retrograde semaphorin 3A signalling regulates the dendritic localization of GluA2-containing AMPA receptors

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

Altered axonal targeting and short-term plasticity in the hippocampus of Disc1 mutant mice

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