Fast transport and retrograde movement of huntingtin and HAP 1 in axons.
Huntingtin, the protein product of the Huntington's disease gene, associates with vesicle membranes and microtubules in neurons. Analysis of axonal transport with a stop-flow, double crush ligation approach in rat sciatic nerve showed that full length huntingtin (350 kDa) and an N-terminal cleavage product (50 kD) were increased within 6-12 h on both the proximal and distal sides of the crush site when compared with normal unligated nerve. The huntingtin associated protein HAP 1 and the retrograde motor protein dynein also accumulated on both sides of the crush, whereas the vesicle docking protein SNAP-25 was elevated only proximally. The cytoskeletal protein alpha-tubulin was unaffected. The rapid anterograde accumulation of huntingtin and HAP 1 is compatible with their axonal transport on vesicular membranes. Retrograde movement of both proteins, as seen by accumulation distal to the nerve crush, may be necessary for their degradation at the soma or for a function in retrograde membrane trafficking.
Block-Galarza
J
J
Department of Medicine, University of Massachusetts Medical School, Worcester 01655, USA.
Chase
K O
KO
Sapp
E
E
Vaughn
K T
KT
Vallee
R B
RB
DiFiglia
M
M
Aronin
N
N
D000818:Animals; D001369:Axons / Q000378:metabolism*; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D000071058:Huntingtin Protein; D008297:Male; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000378:metabolism; D013997:Time Factors
C490758:Hap1 protein, mouse; C490757:Hap1 protein, rat; C506812:Htt protein, mouse; C499524:Htt protein, rat; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins