Fast transport and retrograde movement of huntingtin and... : NeuroReport (original) (raw)

Molecular Neuroscience

Block-Galarza, Jessie1; Chase, Kathryn O.1; Sapp, Ellen2; Vaughn, Kevin T.3; Vallee, Richard B.3; DiFiglia, Marian2; Aronin, Neil1,4

1Departments of Medicine and Cell Biology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA, 01655

2Laboratory of Cellular Neurobiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA

3Worcester Foundation for Experimental Biology, Shrewsbury, MA 01545, USA

4Corresponding Author: Neil Aronin: Departments of Medicine and Cell Biology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA, 01655

ACKNOWLEDGEMENTS: This work was supported by National Institutes of Health grants NS31579 to N.A. and M.D., NS 16367 to M.D., GM47434 to R.B.V., and a Medical Foundation Grant to K.T.V., and grants from the Hereditary Disease Foundation to N.A. and M.D.

Received 14 April 1997; accepted 7 May 1997

Abstract

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 a-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.