DISC1-kendrin interaction is involved in centrosomal microtubule network formation

Biochem Biophys Res Commun. 2008 Dec 26;377(4):1051-6. doi: 10.1016/j.bbrc.2008.10.100. Epub 2008 Oct 26.

Abstract

Disrupted-In-Schizophrenia 1 (DISC1) was identified as a novel gene disrupted by a (1;11)(q42.1;q14.3) translocation segregating with schizophrenia, bipolar disorder and other major mental illnesses in a Scottish family. We previously identified 446-533 amino acids of DISC1 as the kendrin-binding region by means of a directed yeast two-hybrid interaction assay and showed that the DISC1-kendrin interaction is indispensable for the centrosomal localization of DISC1. In this study, to confirm the DISC1-kendrin interaction, we examined the interaction between deletion mutants of DISC1 and kendrin. Then, we demonstrated that the carboxy-terminus of DISC1 is indispensable for the interaction with kendrin. Furthermore, the immunocytochemistry revealed that the carboxy-terminus of DISC1 is also required for the centrosomal targeting of DISC1. Overexpression of the DISC1-binding region of kendrin or the DISC1 deletion mutant lacking the kendrin-binding region impairs the microtubule organization. These findings suggest that the DISC1-kendrin interaction plays a key role in the microtubule dynamics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • COS Cells
  • Calmodulin-Binding Proteins / metabolism*
  • Centrosome / metabolism*
  • Centrosome / ultrastructure
  • Chlorocebus aethiops
  • Humans
  • Immunoprecipitation
  • Microtubules / metabolism*
  • Microtubules / ultrastructure
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Protein Structure, Tertiary
  • Sequence Deletion

Substances

  • Calmodulin-Binding Proteins
  • DISC1 protein, human
  • Nerve Tissue Proteins
  • kendrin