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GAP-43 is key to mitotic spindle control and centrosome-based polarization in neurons

Rashmi Mishra, Shailesh Kumar Gupta, Karina F. Meiri, Megin Fong, Peter Thostrup, David Juncker and Shyamala Mani

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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

Rashmi Mishra

National Brain Research Center; Manesar, Haryana, India

Shailesh Kumar Gupta

National Brain Research Center; Manesar, Haryana, India

Karina F. Meiri

Tufts University School of Medicine; Boston, MA

Megin Fong

McGill University; Montreal, Canada

Peter Thostrup

McGill University; Montreal, Canada

David Juncker

McGill University; Montreal, Canada

Shyamala Mani

National Brain Research Center; Manesar, India

This is an open-access article

 Download PDF

If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.