CRMP-2 is involved in kinesin-1-dependent transport of the Sra-1/WAVE1 complex and axon formation.
A neuron has two types of highly polarized cell processes, the single axon and multiple dendrites. One of the fundamental questions of neurobiology is how neurons acquire such specific and polarized morphologies. During neuronal development, various actin-binding proteins regulate dynamics of actin cytoskeleton in the growth cones of developing axons. The regulation of actin cytoskeleton in the growth cones is thought to be involved in axon outgrowth and axon-dendrite specification. However, it is largely unknown which actin-binding proteins are involved in axon-dendrite specification and how they are transported into the developing axons. We have previously reported that collapsin response mediator protein 2 (CRMP-2) plays a critical role in axon outgrowth and axon-dendrite specification (N. Inagaki, K. Chihara, N. Arimura, C. Menager, Y. Kawano, N. Matsuo, T. Nishimura, M. Amano, and K. Kaibuchi, Nat. Neurosci. 4:781-782, 2001). Here, we found that CRMP-2 interacted with the specifically Rac1-associated protein 1 (Sra-1)/WASP family verprolin-homologous protein 1 (WAVE1) complex, which is a regulator of actin cytoskeleton. The knockdown of Sra-1 and WAVE1 by RNA interference canceled CRMP-2-induced axon outgrowth and multiple-axon formation in cultured hippocampal neurons. We also found that CRMP-2 interacted with the light chain of kinesin-1 and linked kinesin-1 to the Sra-1/WAVE1 complex. The knockdown of CRMP-2 and kinesin-1 delocalized Sra-1 and WAVE1 from the growth cones of axons. These results suggest that CRMP-2 transports the Sra-1/WAVE1 complex to axons in a kinesin-1-dependent manner and thereby regulates axon outgrowth and formation.
Kawano
Yoji
Y
Department of Cell Pharmacology, Graduate School of Medicine, Nagoya University, 65 Tsurumai, Showa-ku, Nagoya, Aichi 466-8550, Japan.
Yoshimura
Takeshi
T
Tsuboi
Daisuke
D
Kawabata
Saeko
S
Kaneko-Kawano
Takako
T
Shirataki
Hiromichi
H
Takenawa
Tadaomi
T
Kaibuchi
Kozo
K
D000199:Actins / Q000737:chemistry; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001369:Axons / Q000378:metabolism*; D017173:Caenorhabditis elegans; D002478:Cells, Cultured; D002846:Chromatography, Affinity; D003599:Cytoskeleton / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D003712:Dendrites / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D007313:Insecta; D036341:Intercellular Signaling Peptides and Proteins; D016547:Kinesins / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009474:Neurons / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D013552:Swine; D014162:Transfection; D051300:Wiskott-Aldrich Syndrome Protein Family / Q000378:metabolism*
D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; C109916:CYFIP1 protein, human; D018076:DNA, Complementary; D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; D051300:Wiskott-Aldrich Syndrome Protein Family; C095114:collapsin response mediator protein-2; D005982:Glutathione Transferase; D016547:Kinesins