Cyclin-Dependent Kinase 5 Permits Efficient Cytoskeletal Remodeling—a Hypothesis on Neuronal Migration
1 Department of Pathology, Harvard Medical School, Boston, MA 02115, USA, 2 Howard Hughes Medical Institute, Boston, MA 02115, USA and 3 Program in Neuroscience, Harvard University, Boston, MA 02115, USA
Address correspondence to Zhigang Xie, Department of Pathology, Harvard Medical School, New Research Building, Floors 8 & 9, 77 Avenue Louis Pasteur, Boston, MA 02115, USA. Email: zhigang_xie{at}hms.harvard.edu, li-huei_tsai{at}hms.harvard.edu.
Migration of neurons to their proper position underlies mammalian brain development. To remain on the proper path, a migrating neuron needs to detect various external signals and respond by efficiently remodeling its cytoskeleton. Cyclin-dependent kinase 5 (Cdk5), a member of the cyclin-dependent kinase family, regulates neuronal migration by phosphorylating a number of intracellular substrates. Deficiencies in Cdk5 preferentially cause impairments in radial glia–guided migration, a process that involves complex remodeling of the cytoskeleton, particularly the microtubules. Furthermore, the defined substrates of Cdk5 that are important for migration generally link Cdk5 to the cytoskeleton. Interestingly, none of these phosphorylation events seem to directly control the activity of the substrates. Taken together, these findings support a model in which Cdk5 does not directly control the detection of any specific external signals but instead regulates efficient remodeling of the cytoskeleton through phosphorylation of multiple substrates.
Key Words: cyclin-dependent kinase 5 • migration • microtubules
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  I. Alvarez-Tabares and J. Perez-Martin Cdk5 kinase regulates the association between adaptor protein Bem1 and GEF Cdc24 in the fungus Ustilago maydis J. Cell Sci., September 1, 2008; 121(17): 2824 - 2832. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Pandithage, R. Lilischkis, K. Harting, A. Wolf, B. Jedamzik, J. Luscher-Firzlaff, J. Vervoorts, E. Lasonder, E. Kremmer, B. Knoll, et al. The regulation of SIRT2 function by cyclin-dependent kinases affects cell motility J. Cell Biol., March 5, 2008; 180(5): 915 - 929. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Hirota, T. Ohshima, N. Kaneko, M. Ikeda, T. Iwasato, A. B. Kulkarni, K. Mikoshiba, H. Okano, and K. Sawamoto Cyclin-Dependent Kinase 5 Is Required for Control of Neuroblast Migration in the Postnatal Subventricular Zone J. Neurosci., November 21, 2007; 27(47): 12829 - 12838. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Causeret, T. Jacobs, M. Terao, O. Heath, M. Hoshino, and M. Nikolic Neurabin-I Is Phosphorylated by Cdk5: Implications for Neuronal Morphogenesis and Cortical Migration Mol. Biol. Cell, November 1, 2007; 18(11): 4327 - 4342. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Flor-Parra, S. Castillo-Lluva, and J. Perez-Martin Polar Growth in the Infectious Hyphae of the Phytopathogen Ustilago maydis Depends on a Virulence-Specific Cyclin PLANT CELL, October 1, 2007; 19(10): 3280 - 3296. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Castillo-Lluva, I. Alvarez-Tabares, I. Weber, G. Steinberg, and J. Perez-Martin Sustained cell polarity and virulence in the phytopathogenic fungus Ustilago maydis depends on an essential cyclin-dependent kinase from the Cdk5/Pho85 family J. Cell Sci., May 1, 2007; 120(9): 1584 - 1595. [Abstract] [Full Text] [PDF]
|
|