Cis and trans interactions of L1 with neuropilin-1 control axonal responses to semaphorin 3A

Castellani, Valérie; Angelis, Elena De; Kenwrick, Susan; Rougon, Geneviève

doi:10.1093/emboj/cdf645

Cited by 203 publications

(179 citation statements)

References 35 publications

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“…Notably, CHL1 interacts with semaphorin 3A during neurite outgrowth and growth cone collapse (53,54). Intriguingly, soluble L1 converts Sema3A-induced axonal repulsion into attraction (55,56). Given the close similarity between CHL1 and L1, soluble CHL1 may also regulate Sema3A-induced axonal repulsion and attraction.…”

Section: Discussionmentioning

confidence: 99%

β-Site Amyloid Precursor Protein (APP)-cleaving Enzyme 1 (BACE1)-deficient Mice Exhibit a Close Homolog of L1 (CHL1) Loss-of-function Phenotype Involving Axon Guidance Defects

Hitt¹,

Riordan²,

Kukreja

et al. 2012

Journal of Biological Chemistry

137

151

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Background:Little is known about BACE1 functions. Results: BACE1 Ϫ/Ϫ mice have axon guidance defects similar to those of CHL1 Ϫ/Ϫ mice; CHL1 undergoes BACE1-dependent processing in vivo; CHL1 and BACE1 co-localize in terminals and growth cones. Conclusion: BACE1 deficiency produces a CHL1 loss-of-function phenotype. Significance: BACE1 inhibition may cause axon guidance defects, adding a note of caution to BACE1 inhibitor drug development.

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Section: Discussionmentioning

confidence: 99%

β-Site Amyloid Precursor Protein (APP)-cleaving Enzyme 1 (BACE1)-deficient Mice Exhibit a Close Homolog of L1 (CHL1) Loss-of-function Phenotype Involving Axon Guidance Defects

Hitt¹,

Riordan²,

Kukreja

et al. 2012

Journal of Biological Chemistry

137

151

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“…The pro-migratory effect of Sema3A on GBM cells could possibly be linked to the intracellular availability and localization of cGMP as well. Other factors on the cell surface, such as L1-CAM, could modulate Sema3A effects and shift neuronal migration response from repulsion to attraction (Castellani et al, 2000(Castellani et al, , 2002. Therefore, functional studies addressing the role of L1-CAM and cGMP in Sema3A-mediated GBM cell migration will be crucial to further understand Sema3A signaling in GBMs.…”

Section: Discussionmentioning

confidence: 99%

Autocrine semaphorin 3A signaling promotes glioblastoma dispersal

et al. 2009

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Glioblastoma multiforme (GBM) is the most malignant glioma type with diffuse borders due to extensive tumor cell infiltration. Therefore, understanding the mechanism of GBM cell dispersal is critical for developing effective therapies to limit infiltration. We identified neuropilin-1 as a mediator of cancer cell invasion by a functional proteomic screen and showed its role in GBM cells. Neuropilin-1 is a receptor for semaphorin3A (Sema3A), a secreted chemorepellent that facilitates axon guidance during neural development. Although neuropilin-1 expression in GBMs was previously shown, its role as a Sema3A receptor remained elusive. Using fluorophore-assisted light inactivation and RNA interference , we showed that neuropilin-1 is required for GBM cell migration. We also showed that GBM cells secrete Sema3A endogenously, and RNA interferencemediated downregulation of Sema3A inhibits migration and alters cell morphology that is dependent on Rac1 activity. Sema3A depletion also reduces dispersal, which is recovered by supplying Sema3A exogenously. Extracellular application of Sema3A decreases cell-substrate adhesion in a neuropilin-1-dependent manner. Using immunohistochemistry, we showed that Sema3A is overexpressed in a subset of human GBMs compared with the non-neoplastic brain. Together, these findings implicate Sema3A as an autocrine signal for neuropilin-1 to promote GBM dispersal by modulating substrate adhesion and suggest that targeting Sema3A-neuropilin-1 signaling may limit GBM infiltration.

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“…Other genes we identified as hypoxia regulated in nonrenal cell lines have roles that could contribute to the malignant phenotype, including cell adhesion and VEGF presentation, L1CAM (Castellani et al, 2002), iron metabolism or gelling of the actin cytoskeleton, transgelin.…”

Section: Discussionmentioning

confidence: 99%

Gene array of VHL mutation and hypoxia shows novel hypoxia-induced genes and that cyclin D1 is a VHL target gene

et al. 2004

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Gene expression analysis was performed on a human renal cancer cell line (786-0) with mutated VHL gene and a transfectant with wild-type VHL to analyse genes regulated by VHL and to compare with the gene programme regulated by hypoxia. There was a highly significant concordance of the global gene response to hypoxia and genes suppressed by VHL. Cyclin D1 was the most highly inducible transcript and 14-3-3 epsilon was downregulated. There were some genes regulated by VHL but not hypoxia in the renal cell line, suggesting a VHL role independent of hypoxia. However in nonrenal cell lines they were hypoxia regulated. These included several new pathways regulated by hypoxia, including RNase 6PL, collagen type 1 alpha 1, integrin alpha 5, ferritin light polypeptide, JM4 protein, transgelin and L1 cell adhesion molecule. These were not found in a recent SAGE analysis of the same cell line. Hypoxia induced downregulation of Cyclin D1 in nonrenal cells via an HIF independent pathway. The selective regulation of Cyclin D1 by hypoxia in renal cells may therefore contribute to the tissue selectivity of VHL mutation.

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Cis and trans interactions of L1 with neuropilin-1 control axonal responses to semaphorin 3A

Cited by 203 publications

References 35 publications

β-Site Amyloid Precursor Protein (APP)-cleaving Enzyme 1 (BACE1)-deficient Mice Exhibit a Close Homolog of L1 (CHL1) Loss-of-function Phenotype Involving Axon Guidance Defects

β-Site Amyloid Precursor Protein (APP)-cleaving Enzyme 1 (BACE1)-deficient Mice Exhibit a Close Homolog of L1 (CHL1) Loss-of-function Phenotype Involving Axon Guidance Defects

Autocrine semaphorin 3A signaling promotes glioblastoma dispersal

Gene array of VHL mutation and hypoxia shows novel hypoxia-induced genes and that cyclin D1 is a VHL target gene

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