Misregulation of microtubule dynamics in autism

  • Awarded: 2013
  • Award Type: Explorer
  • Award #: 296143

KATNAL2 is a recently identified autism gene that is predicted to code for a microtubule-severing enzyme. However, researchers don’t know how this gene is involved in brain development or what cellular events in the developing brain go awry if it is mutated. Xiaobing Yuan and Peter Baas are studying whether KATNAL2 and other autism genes play an essential role in neuronal migration through the regulation of microtubule dynamics.

They found that KATNAL2 does not seem to be a microtubule-severing protein and may not play an important role in neuronal migration. KATNAL2 proteins distribute at the centrosome-related structures, including the centrosome and the mid-body of mitotic neural progenitor cells and several other cell types, and its expression is markedly upregulated when cells enter the cell division cycle.

Mutation of centrosome components has been linked to several developmental disorders and psychiatric diseases. These preliminary findings further implicate centrosome-related proteins in neuropsychiatric disorders.

Based on these findings, future studies of how KATNAL2 mutations lead to autism should be directed toward clarifying the gene’s role in the centrosome-related signaling pathway that regulates neurogenesis rather than neuronal migration.

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