Plexin-A2 and its ligand, Sema6A, control nucleus-centrosome coupling in migrating granule cells.
Cell-Movement, Cell-Nucleus, Cells-Cultured, Centrosome, Cerebellum, Gene-Expression-Regulation-Developmental, Mice-Inbred-C57BL, Mice-Knockout, Nerve-Tissue-Proteins, Neurons, Receptors-Cell-Surface
Nat Neurosci 2008 Apr; 11(4):440-9.
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.
Renaud, J; Kerjan, G; Sumita, I; Zagar, Y; Georget, V; Kim, D; Fouquet, C; Suda, K; Sanbo, M; Suto, F; Ackerman, S L.; Mitchell, K J.; Fujisawa, H; and Chedotal, A, "Plexin-A2 and its ligand, Sema6A, control nucleus-centrosome coupling in migrating granule cells." (2008). Faculty Research 2000 - 2009. 1764.