Cayman ataxia protein caytaxin is transported by kinesin along neurites through binding to kinesin light chains.
Deficiency of caytaxin results in hereditary ataxia or dystonia in humans, mice and rats. Our yeast two-hybrid screen identified kinesin light chains (KLCs) as caytaxin-binding proteins. The tetratricopeptide-repeat region of KLC1 recognizes the ELEWED sequence (amino acids 115-120) of caytaxin. This motif is conserved among BNIP-2 family members and other KLC-interacting kinesin cargo proteins such as calsyntenins. Caytaxin associates with kinesin heavy chains (KHCs) indirectly by binding to KLCs, suggesting that caytaxin binds to the tetrameric kinesin molecule. In cultured hippocampal neurons, we found that caytaxin is distributed in both axons and dendrites in punctate patterns, and it colocalizes with microtubules and KHC. GFP-caytaxin expressed in hippocampal neurons is transported at a speed ( approximately 1 mum/second) compatible with kinesin movement. Inhibition of kinesin-1 by dominant-negative KHC decreases the accumulation of caytaxin in the growth cone. Caytaxin puncta do not coincide with vesicles containing known kinesin cargos such as APP or JIP-1. A part of caytaxin, however, colocalizes with mitochondria and suppression of caytaxin expression by RNAi redistributes mitochondria away from the distal ends of neurites. These data indicate that caytaxin binds to kinesin-1 and functions as an adaptor that mediates intracellular transport of specific cargos, one of which is the mitochondrion.
Aoyama
Takane
T
Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara 630-0192, Japan.
Hata
Suguru
S
Nakao
Takeshi
T
Tanigawa
Yuka
Y
Oka
Chio
C
Kawaichi
Masashi
M
D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology; D020816:Amino Acid Motifs; D016564:Amyloid beta-Protein Precursor / Q000502:physiology; D000818:Animals; D001259:Ataxia; D001370:Axonal Transport / Q000502:physiology*; D001665:Binding Sites; D002460:Cell Line; D006624:Hippocampus; D006801:Humans; D016547:Kinesins / Q000737:chemistry / Q000502:physiology*; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000737:chemistry / Q000502:physiology; D008870:Microtubules / Q000502:physiology; D008928:Mitochondria / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000502:physiology*; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D058255:Protease Nexins; D021122:Protein Subunits / Q000737:chemistry / Q000502:physiology; D034622:RNA Interference; D051381:Rats; D011956:Receptors, Cell Surface / Q000502:physiology; D020798:Two-Hybrid System Techniques
C545487:APP protein, human; D048868:Adaptor Proteins, Signal Transducing; D016564:Amyloid beta-Protein Precursor; C518021:Atcay protein, mouse; C000715688:KLC1 protein, human; C000715690:Klc1 protein, rat; C000715695:Kns2 protein, mouse; C490666:MAPK8IP1 protein, human; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D058255:Protease Nexins; D021122:Protein Subunits; D011956:Receptors, Cell Surface; C508764:atcay protein, rat; D016547:Kinesins