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Plexin-A2 and its ligand, Sema6A, control nucleus-centrosome coupling in migrating granule cells.

Nature neuroscience | Apr 27, 2008

http://www.ncbi.nlm.nih.gov/pubmed/18327254

During their migration, cerebellar granule cells switch from a tangential to a radial mode of migration. We have previously demonstrated that this involves the transmembrane semaphorin Sema6A. We show here that plexin-A2 is the receptor that controls Sema6A function in migrating granule cells. In plexin-A2-deficient (Plxna2(-/-)) mice, which were generated by homologous recombination, many granule cells remained in the molecular layer, as we saw in Sema6a mutants. A similar phenotype was observed in mutant mice that were generated by mutagenesis with N-ethyl-N-nitrosourea and had a single amino-acid substitution in the semaphorin domain of plexin-A2. We found that this mutation abolished the ability of Sema6A to bind to plexin-A2. Mouse chimera studies further suggested that plexin-A2 acts in a cell-autonomous manner. We also provide genetic evidence for a ligand-receptor relationship between Sema6A and plexin-A2 in this system. Using time-lapse video microscopy, we found that centrosome-nucleus coupling and coordinated motility were strongly perturbed in Sema6a(-/-) and Plxna2(-/-) granule cells. This suggests that semaphorin-plexin signaling modulates cell migration by controlling centrosome positioning.

Pubmed ID: 18327254 RIS Download

Mesh terms: Animals | Cell Movement | Cell Nucleus | Cells, Cultured | Centrosome | Cerebellum | Gene Expression Regulation, Developmental | In Vitro Techniques | Mice | Mice, Inbred C57BL | Mice, Knockout | Nerve Tissue Proteins | Neurons | Receptors, Cell Surface | Semaphorins

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Associated grants

  • Agency: NINDS NIH HHS, Id: NS041215
  • Agency: NINDS NIH HHS, Id: NS35900
  • Agency: Howard Hughes Medical Institute, Id:

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