CRMP-2 directly binds to cytoplasmic dynein and interferes with its activity.
The active transport of proteins and organelles is critical for cellular organization and function in eukaryotic cells. A substantial portion of long-distance transport depends on the opposite polarity of the kinesin and dynein family molecular motors to move cargo along microtubules. It is increasingly clear that many cargo molecules are moved bi-directionally by both sets of motors; however, the regulatory mechanism that determines the directionality of transport remains unclear. We previously reported that collapsin response mediator protein-2 (CRMP-2) played key roles in axon elongation and neuronal polarization. CRMP-2 was also found to associate with the anterograde motor protein Kinesin-1 and was transported with other cargoes toward the axon terminal. In this study, we investigated the association of CRMP-2 with a retrograde motor protein, cytoplasmic dynein. Immunoprecipitation assays showed that CRMP-2 interacted with cytoplasmic dynein heavy chain. Dynein heavy chain directly bound to the N-terminus of CRMP-2, which is the distinct side of CRMP-2's kinesin light chain-binding region. Furthermore, over-expression of the dynein-binding fragments of CRMP-2 prevented dynein-driven microtubule transport in COS-7 cells. Given that CRMP-2 is a key regulator of axon elongation, this interference with cytoplasmic dynein function by CRMP-2 might have an important role in axon formation, and neuronal development.
Arimura
Nariko
N
Department of Cell Pharmacology, Nagoya University Graduate School of Medicine, Showa, Nagoya, Japan.
Hattori
Atsushi
A
Kimura
Toshihide
T
Nakamuta
Shinichi
S
Funahashi
Yasuhiro
Y
Hirotsune
Shinji
S
Furuta
Kenya
K
Urano
Takashi
T
Toyoshima
Yoko Y
YY
Kaibuchi
Kozo
K
D000818:Animals; D001369:Axons / Q000378:metabolism*; D001693:Biological Transport, Active / Q000502:physiology; D019556:COS Cells; D002522:Chlorocebus aethiops; D003593:Cytoplasm / Q000378:metabolism; D004398:Dyneins / Q000737:chemistry / Q000378:metabolism*; D020439:Growth Cones / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary; D051381:Rats; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014162:Transfection
D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D011994:Recombinant Proteins; C095114:collapsin response mediator protein-2; D004398:Dyneins