Kinesin superfamily protein 2A (KIF2A) functions in suppression of collateral branch extension

Cell. 2003 Jul 25;114(2):229-39. doi: 10.1016/s0092-8674(03)00522-1.

Abstract

Through interactions with microtubules, the kinesin superfamily of proteins (KIFs) could have multiple roles in neuronal function and development. During neuronal development, postmitotic neurons develop primary axons extending toward targets, while other collateral branches remain short. Although the process of collateral branching is important for correct wiring of the brain, the mechanisms involved are not well understood. In this study, we analyzed kif2a(-/-) mice, whose brains showed multiple phenotypes, including aberrant axonal branching due to overextension of collateral branches. In kif2a(-/-) growth cones, microtubule-depolymerizing activity decreased. Moreover, many individual microtubules showed abnormal behavior at the kif2a(-/-) cell edge. Based on these results, we propose that KIF2A regulates microtubule dynamics at the growth cone edge by depolymerizing microtubules and that it plays an important role in the suppression of collateral branch extension.

Publication types

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

MeSH terms

  • Animals
  • Axons / physiology*
  • Axons / ultrastructure
  • Brain / abnormalities
  • Cells, Cultured
  • Chimera
  • Crosses, Genetic
  • Female
  • Growth Cones / physiology
  • Hippocampus / cytology
  • Kinesins / physiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microtubules / physiology*
  • Microtubules / ultrastructure
  • Nerve Tissue Proteins
  • Neuroglia / metabolism
  • Neurons / cytology
  • Recombination, Genetic
  • Repressor Proteins
  • Tubulin / metabolism

Substances

  • Kif2b protein, mouse
  • Nerve Tissue Proteins
  • Repressor Proteins
  • Tubulin
  • KIF2A protein, mouse
  • Kinesins