title: GAP-43 is key to mitotic spindle control and centrosome-based polarization in neurons.
abstract: In neurons, the position of the centrosome during final mitosis marks the point of emergence of the future axon. However, the molecular underpinnings linking centrosome position to axon emergence are unknown. GAP-43 is a calmodulin-binding IQ motif protein that regulates neuronal cytoskeletal architecture by interacting with F-actin in a phosphorylation dependent manner. Here we show that GAP-43 is associated with the centrosome and plays a critical role in mitosis and acquisition of neuronal polarity in cerebellar granule neurons. In the absence of GAP-43, the centrosome position is delinked from process outgrowth and is only capable of mediating morphological polarization, however molecular specification of the axonal compartment does not take place. These results show that GAP-43 is required to link centrosome position to process outgrowth in order to generate neuronal polarity in cerebellar granule cells.
authors.affiliation: National Brain Research Center, Manesar, Haryana, India.
authors.forename: Rashmi
authors.initials: R
authors.lastname: Mishra
authors.forename: Shailesh Kumar
authors.initials: SK
authors.lastname: Gupta
authors.forename: Karina F
authors.initials: KF
authors.lastname: Meiri
authors.forename: Megin
authors.initials: M
authors.lastname: Fong
authors.forename: Peter
authors.initials: P
authors.lastname: Thostrup
authors.forename: David
authors.initials: D
authors.lastname: Juncker
authors.forename: Shyamala
authors.initials: S
authors.lastname: Mani
mesh_terms: D000818:Animals; D016764:Cell Polarity / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D018385:Centrosome / Q000502:physiology*; D002531:Cerebellum / Q000166:cytology / Q000473:pathology / Q000502:physiology; D019922:GAP-43 Protein / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D008941:Spindle Apparatus / Q000502:physiology*
chemical_list: D019922:GAP-43 Protein