The Doublecortin Gene Family and Disorders of Neuronal Structure

The doublecortin gene family is associated with subcortical band heterotopia, lissencephaly, epilepsy, developmental dyslexia and retinitis pigmentosa. At least 11 genes homologous to the doublecortin gene exist in humans and mice. Cellular processes regulated by different members of the doublecortin family involve neuronal migration, neurogenesis and eye receptor development. Underlying mechanisms include regulation of cytoskeletal structure and microtubule-based transport. Through their doublecortin-domains, doublecortin proteins can bind microtubules and regulate microtubule-dependent processes. However, this regulation is complex and involves many interacting proteins. Moreover, different spatiotemporal expression patterns and the generation of splice variants further contribute to this complexity. The doublecortin-like kinase 1 gene in particular, produces splice variants with different protein domains such as doublecortin-domains, a serine, threonine and proline-rich domain and a serine/threonine kinase-domain. Here, we review our current knowledge on the doublecortin gene family with an emphasis on proteins interacting with doublecortin domains and other domains. In addition, to generate new hypotheses for further research, we analyzed the serine, threonine and proline-rich domain for predicted protein interactions.