DCAMKL1 encodes a protein kinase with homology to doublecortin that regulates microtubule polymerization

Doublecortin (DCX) is a microtubule-associated protein required for neurona l 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 contain s an additional 360 amino acid C-terminal domain encoding a putative Ca2+/c almodulin-dependent protein kinase. The homology to DCX suggested that DCAM KL1 may regulate microtubules, as well as mediate a phosphorylation-depende nt signal transduction pathway. Here we show that DCAMKL1 is expressed thro ughout the CNS and PNS in migrating neuronal populations and overlaps in it s expression with DCX and microtubules. Purified DCAMKL1 associates with mi crotubules and stimulates polymerization of purified tubulin and the format ion of aster-like microtubule structures. Overexpressed DCAMKL1 leads to st riking 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 prot ein remain dynamic. DCAMKL1 also encodes a functional kinase capable of pho sphorylating myelin basic protein and itself. However, elimination of the k inase activity of DCAMKL1 has no detectable effect on its microtubule polym erization activity. Because DCAMKL1 is coexpressed with DCX, the two protei ns form a potentially mutually regulatory network linking calcium signaling and microtubule dynamics.