Plexin-A2 and its ligand, Sema6A, control nucleus-centrosome coupling in migrating granule cells.
Document Type
Article
Publication Date
2008
Keywords
Cell-Movement, Cell-Nucleus, Cells-Cultured, Centrosome, Cerebellum, Gene-Expression-Regulation-Developmental, Mice-Inbred-C57BL, Mice-Knockout, Nerve-Tissue-Proteins, Neurons, Receptors-Cell-Surface
First Page
440
Last Page
449
JAX Source
Nat Neurosci 2008 Apr; 11(4):440-9.
Abstract
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.
Recommended Citation
Renaud J,
Kerjan G,
Sumita I,
Zagar Y,
Georget V,
Kim D,
Fouquet C,
Suda K,
Sanbo M,
Suto F,
Ackerman SL,
Mitchell KJ,
Fujisawa H,
Chedotal A.
Plexin-A2 and its ligand, Sema6A, control nucleus-centrosome coupling in migrating granule cells. Nat Neurosci 2008 Apr; 11(4):440-9.