HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: fj.07-103887v1 22/9/3348    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Wong, S. L. A. Articles by Chan, H. Y. E. Search for Related Content PubMed PubMed Citation Articles by Wong, S. L. A. Articles by Chan, H. Y. E.

Sodium dodecyl sulfate-insoluble oligomers are involved in polyglutamine degeneration

S. L. Alan Wong^*,, Wing Man Chan^*, and H. Y. Edwin Chan^*,,,1

^* Laboratory of Drosophila Research,

Molecular Biotechnology Programme, and

Department of Biochemistry, The Chinese University of Hong Kong, Hong Kong, China

¹Correspondence: Department of Biochemistry, The Chinese University of Hong Kong, Shatin N.T., Hong Kong, China. E-mail: hyechan{at}cuhk.edu.hk

In polyglutamine (polyQ) degeneration, disease protein that carries an expanded polyQ tract is neurotoxic. Expanded polyQ protein exists in different conformations that display distinct solubility properties. In this study, an inducible transgenic Drosophila model is established to define the pathogenic form of polyQ protein at an early stage of degeneration in vivo. We show that microscopic polyQ aggregates are neither pathogenic nor protective. Further, no toxic effect of sodium dodecyl sulfate (SDS) -soluble polyQ protein is observed in our model. By means of filtration, 2 forms of SDS-insoluble protein species are identified according to their size. Coexpression of an ATPase-defective form of the molecular chaperone Hsc70 (Hsc70-K71S) selectively reduces the abundance of the large SDS-insoluble polyQ species, but such modulation has no modifying effects on degeneration. Notably, we detect a distinct Hsc70-K71S-resistant, small, SDS-insoluble polyQ oligomeric species that is closely correlated with degeneration. Our data highlight the toxic role of SDS-insoluble oligomers in polyQ degeneration in vivo.—Wong, S. L. A., Chan, W. M., and Chan, H. Y. E. Sodium dodecyl sulfate-insoluble oligomers are involved in polyglutamine degeneration.

Key Words: aggregate • Drosophila • neurodegeneration • solubility