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PMID:19861499

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Citation

Aoyama, T, Hata, S, Nakao, T, Tanigawa, Y, Oka, C and Kawaichi, M (2009) Cayman ataxia protein caytaxin is transported by kinesin along neurites through binding to kinesin light chains. J. Cell. Sci. 122:4177-85

Abstract

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.

Links

PubMed Online version:10.1242/jcs.048579

Keywords

Adaptor Proteins, Signal Transducing/physiology; Amino Acid Motifs; Amyloid beta-Protein Precursor/physiology; Animals; Ataxia; Axonal Transport/physiology; Binding Sites; Cell Line; Hippocampus; Humans; Kinesin/chemistry; Kinesin/physiology; Mice; Microtubule-Associated Proteins/chemistry; Microtubule-Associated Proteins/physiology; Microtubules/physiology; Mitochondria/physiology; Nerve Tissue Proteins/chemistry; Nerve Tissue Proteins/physiology; Neurons/metabolism; Neurons/ultrastructure; Protease Nexins; Protein Subunits/chemistry; Protein Subunits/physiology; RNA Interference; Rats; Receptors, Cell Surface/physiology; Two-Hybrid System Techniques

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

RAT:KLC1

involved_in

GO:0035418: protein localization to synapse

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:KLC1

involved_in

GO:0006886: intracellular protein transport

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:KLC1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q86WG3

F

Seeded From UniProt

complete

RAT:ATCAY

located_in

GO:0045202: synapse

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:ATCAY

located_in

GO:0030424: axon

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:ATCAY

located_in

GO:0030425: dendrite

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:ATCAY

located_in

GO:0031966: mitochondrial membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:ATCAY

located_in

GO:0043005: neuron projection

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:ATCAY

involved_in

GO:0031175: neuron projection development

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:ATCAY

part_of

GO:0030424: axon

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:ATCAY

part_of

GO:0030425: dendrite

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:ATCAY

involved_in

GO:0031175: neuron projection development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:ATCAY

part_of

GO:0045202: synapse

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:ATCAY

involved_in

GO:0048311: mitochondrion distribution

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:ATCAY

enables

GO:0019894: kinesin binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q07866

F

Seeded From UniProt

complete


See also

References

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