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The Journal of Neuroscience, December 15, 2000, 20(24):9152-9161
DCAMKL1 Encodes a Protein Kinase with Homology to Doublecortin that Regulates Microtubule Polymerization
Peter T. Lin1, Joseph G. Gleeson1, Joseph C. Corbo1, Lisa Flanagan2, and Christopher A. Walsh1 1 Division of Neurogenetics, Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, 02115, and 2 Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, 02115
Doublecortin (DCX) is a microtubule-associated protein required for neuronal migration to the cerebral cortex. DCAMKL1 consists of an N terminus that is 65% similar to DCX throughout the entire length of DCX, but also contains an additional 360 amino acid C-terminal domain encoding a putative Ca2+/calmodulin-dependent protein kinase. The homology to DCX suggested that DCAMKL1 may regulate microtubules, as well as mediate a phosphorylation-dependent signal transduction pathway. Here we show that DCAMKL1 is expressed throughout the CNS and PNS in migrating neuronal populations and overlaps in its expression with DCX and microtubules. Purified DCAMKL1 associates with microtubules and stimulates polymerization of purified tubulin and the formation of aster-like microtubule structures. Overexpressed DCAMKL1 leads to striking microtubule bundling in cell lines and cultured primary neural cells. Time-lapse imaging of cells transfected with a DCAMKL1-green fluorescent protein fusion protein shows that the microtubules associated with the protein remain dynamic. DCAMKL1 also encodes a functional kinase capable of phosphorylating myelin basic protein and itself. However, elimination of the kinase activity of DCAMKL1 has no detectable effect on its microtubule polymerization activity. Because DCAMKL1 is coexpressed with DCX, the two proteins form a potentially mutually regulatory network linking calcium signaling and microtubule dynamics.
Key words: neuronal migration; microtubule; kinase; microtubule-associated protein; doublecortin; lissencephaly
Copyright © 2000 Society for Neuroscience 0270-6474/00/20249152-10$05.00/0
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