GSK-3beta-regulated interaction of BICD with dynein is involved in microtubule anchorage at centrosome

EMBO J. 2006 Dec 13;25(24):5670-82. doi: 10.1038/sj.emboj.7601459. Epub 2006 Nov 30.

Abstract

Microtubule arrays direct intracellular organization and define cellular polarity. Here, we show a novel function of glycogen synthase kinase-3beta (GSK-3beta) in the organization of microtubule arrays through the interaction with Bicaudal-D (BICD). BICD is known to form a complex with dynein-dynactin and to function in the intracellular vesicle trafficking. Our data revealed that GSK-3beta is required for the binding of BICD to dynein but not to dynactin. Knockdown of GSK-3beta or BICD reduced centrosomally focused microtubules and induced the mislocalization of centrosomal proteins. The unfocused microtubules in GSK-3beta knockdown cells were rescued by the expression of the dynein intermediate chain-BICD fusion protein. Microtubule regrowth assays showed that GSK-3beta and BICD are required for the anchoring of microtubules to the centrosome. These results imply that GSK-3beta may function in transporting centrosomal proteins to the centrosome by stabilizing the BICD1 and dynein complex, resulting in the regulation of a focused microtubule organization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / chemistry
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Amino Acid Sequence
  • Animals
  • CHO Cells
  • Centrosome / metabolism*
  • Cricetinae
  • Cricetulus
  • Cytoskeletal Proteins / chemistry
  • Cytoskeletal Proteins / metabolism*
  • Dyneins / metabolism*
  • Glycogen Synthase Kinase 3 / metabolism*
  • Glycogen Synthase Kinase 3 beta
  • HeLa Cells
  • Humans
  • Microtubules / metabolism*
  • Molecular Sequence Data
  • Nuclear Proteins / metabolism
  • Phosphorylation
  • Protein Binding
  • Protein Transport

Substances

  • Adaptor Proteins, Signal Transducing
  • BICD1 protein, human
  • Cytoskeletal Proteins
  • NIN protein, human
  • Nuclear Proteins
  • GSK3B protein, human
  • Glycogen Synthase Kinase 3 beta
  • Glycogen Synthase Kinase 3
  • Dyneins