DCAMKL1 encodes a protein kinase with homology to doublecortin that regulates microtubule polymerization.
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 Ca(2+)/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.
Lin
P T
PT
Division of Neurogenetics, Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, 02115, USA.
Gleeson
J G
JG
Corbo
J C
JC
Flanagan
L
L
Walsh
C A
CA
D016475:3T3 Cells; D000818:Animals; D000918:Antibody Specificity; D015153:Blotting, Western; D019556:COS Cells; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement; D002490:Central Nervous System / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D003080:Cold Temperature; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D000089742:Doublecortin-Like Kinases; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009479:Neuropeptides / Q000235:genetics* / Q000378:metabolism; D009928:Organ Specificity; D017933:Peripheral Nervous System / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D012160:Retina / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014162:Transfection
C000714328:DCX protein, human; C000714847:Dcx protein, mouse; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D047908:Intracellular Signaling Peptides and Proteins; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D010750:Phosphoproteins; D020033:Protein Isoforms; C117347:DCLK1 protein, human; D000089742:Doublecortin-Like Kinases; C485525:Dclk1 protein, mouse; D017346:Protein Serine-Threonine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases