PT  - JOURNAL ARTICLE
AU  - Zheng-Hong Qin
AU  - Yumei Wang
AU  - Ellen Sapp
AU  - Benjamin Cuiffo
AU  - Erich Wanker
AU  - Michael R. Hayden
AU  - Kimberly B. Kegel
AU  - Neil Aronin
AU  - Marian DiFiglia
TI  - Huntingtin Bodies Sequester Vesicle-Associated Proteins by a Polyproline-Dependent Interaction
AID  - 10.1523/JNEUROSCI.1409-03.2004
DP  - 2004 Jan 07
TA  - The Journal of Neuroscience
PG  - 269--281
VI  - 24
IP  - 1
4099  - http://www.jneurosci.org/content/24/1/269.short
4100  - http://www.jneurosci.org/content/24/1/269.full
SO  - J. Neurosci.2004 Jan 07; 24
AB  - Polyglutamine expansion in the N terminus of huntingtin (htt) causes selective neuronal dysfunction and cell death by unknown mechanisms. Truncated htt expressed in vitro produced htt immunoreactive cytoplasmic bodies (htt bodies). The fibrillar core of the mutant htt body resisted protease treatment and contained cathepsin D, ubiquitin, and heat shock protein (HSP) 40. The shell of the htt body was composed of globules 14-34 nm in diameter and was protease sensitive. HSP70, proteasome, dynamin, and the htt binding partners htt interacting protein 1 (HIP1), SH3-containing Grb2-like protein (SH3GL3), and 14.7K-interacting protein were reduced in their normal location and redistributed to the shell. Removal of a series of prolines adjacent to the polyglutamine region in htt blocked formation of the shell of the htt body and redistribution of dynamin, HIP1, SH3GL3, and proteasome to it. Internalization of transferrin was impaired in cells that formed htt bodies. In cortical neurons of Huntington's disease patients with early stage pathology, dynamin immunoreactivity accumulated in cytoplasmic bodies. Results suggest that accumulation of a nonfibrillar form of mutant htt in the cytoplasm contributes to neuronal dysfunction by sequestering proteins involved in vesicle trafficking.