The doublecortin gene family and disorders of neuronal structure

Cent Nerv Syst Agents Med Chem. 2010 Mar;10(1):32-46. doi: 10.2174/187152410790780118.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alternative Splicing
  • Amino Acid Sequence
  • Animals
  • Classical Lissencephalies and Subcortical Band Heterotopias* / genetics
  • Classical Lissencephalies and Subcortical Band Heterotopias* / pathology
  • Doublecortin Domain Proteins
  • Humans
  • Microtubule-Associated Proteins / genetics*
  • Microtubule-Associated Proteins / metabolism
  • Microtubules / metabolism
  • Molecular Sequence Data
  • Multigene Family*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Nervous System Malformations / genetics
  • Nervous System Malformations / pathology
  • Neurons* / cytology
  • Neurons* / pathology
  • Neuropeptides / genetics*
  • Neuropeptides / metabolism
  • Promoter Regions, Genetic
  • Retinitis Pigmentosa* / genetics
  • Retinitis Pigmentosa* / pathology
  • Sequence Homology, Amino Acid

Substances

  • Doublecortin Domain Proteins
  • Microtubule-Associated Proteins
  • Nerve Tissue Proteins
  • Neuropeptides