Tubulin and CRMP-2 complex is transported via Kinesin-1.
The transport of tubulin and microtubules in a growing axon is essential for axonal growth and maintenance. However, the molecular mechanism underlying the linkage of tubulin and microtubules to motor proteins is not yet clear. Collapsin response mediator protein-2 (CRMP-2) is enriched at the distal part of growing axons in primary hippocampal neurons and plays a critical role in axon differentiation through its interaction with tubulin dimer and Numb. In this study, we show that CRMP-2 regulates tubulin transport by linking tubulin and Kinesin-1. The C-terminal region of CRMP-2 directly binds to the tetratricopeptide repeat domain of kinesin light chain 1 (KLC1). Soluble tubulin binds to the middle of CRMP-2 and forms a trimeric complex with CRMP-2/KLC1. Furthermore, the movement of GFP-tubulin in the photobleached area is weakened by knockdown of KLCs or CRMP-2. These results indicate that the CRMP-2/Kinesin-1 complex regulates soluble tubulin transport to the distal part of the growing axon.
Kimura
Toshihide
T
Department of Cell Pharmacology, Graduate School of Medicine, Nagoya University, Showa-ku, Nagoya, Aichi, Japan.
Watanabe
Hiroyasu
H
Iwamatsu
Akihiro
A
Kaibuchi
Kozo
K
D000818:Animals; D000831:Animals, Newborn; D001370:Axonal Transport / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D015536:Down-Regulation / Q000502:physiology; D020439:Growth Cones / Q000378:metabolism*; D006624:Hippocampus / Q000196:embryology* / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D016547:Kinesins / Q000378:metabolism*; D046911:Macromolecular Substances / Q000378:metabolism; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism*
D036341:Intercellular Signaling Peptides and Proteins; C000715688:KLC1 protein, human; C000715690:Klc1 protein, rat; C000715695:Kns2 protein, mouse; D046911:Macromolecular Substances; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D011993:Recombinant Fusion Proteins; D014404:Tubulin; C095114:collapsin response mediator protein-2; D016547:Kinesins