SH3GL3 associates with the Huntingtin exon 1 protein and promotes the formation of polygln-containing protein aggregates

A Sittler; S Wälter; N Wedemeyer; R Hasenbank; E Scherzinger; H Eickhoff; G P Bates; H Lehrach; E E Wanker

doi:10.1016/s1097-2765(00)80142-2

SH3GL3 associates with the Huntingtin exon 1 protein and promotes the formation of polygln-containing protein aggregates

Mol Cell. 1998 Oct;2(4):427-36. doi: 10.1016/s1097-2765(00)80142-2.

Authors

A Sittler¹, S Wälter, N Wedemeyer, R Hasenbank, E Scherzinger, H Eickhoff, G P Bates, H Lehrach, E E Wanker

Affiliation

¹ Max-Planck-Institut für Molekulare Genetik, Berlin, Germany.

PMID: 9809064
DOI: 10.1016/s1097-2765(00)80142-2

Abstract

The mechanism by which aggregated polygins cause the selective neurodegeneration in Huntington's disease (HD) is unknown. Here, we show that the SH3GL3 protein, which is preferentially expressed in brain and testis, selectively interacts with the HD exon 1 protein (HDex1p) containing a glutamine repeat in the pathological range and promotes the formation of insoluble polyglutamine-containing aggregates in vivo. The C-terminal SH3 domain in SH3GL3 and the proline-rich region in HDex1p are essential for the interaction. Coimmunoprecipitations and immunofluorescence studies revealed that SH3GL3 and HDex1p colocalize in transfected COS cells. Additionally, an anti-SH3GL3 antibody was also able to coimmunoprecipitate the full-length huntingtin from an HD human brain extract. The characteristics of the interaction between SH3GL3 and huntingtin and the colocalization of the two proteins suggest that SH3GL3 could be involved in the selective neuronal cell death in HD.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adaptor Proteins, Signal Transducing
Animals
Brain Chemistry
COS Cells
Carrier Proteins / genetics*
Carrier Proteins / isolation & purification
Carrier Proteins / metabolism*
Exons / genetics
Gene Expression
Glutamine / genetics*
Glutamine / metabolism
Humans
Huntingtin Protein
Huntington Disease / genetics*
Nerve Tissue Proteins / genetics*
Nerve Tissue Proteins / isolation & purification
Nerve Tissue Proteins / metabolism
Nuclear Proteins / genetics*
Nuclear Proteins / isolation & purification
Nuclear Proteins / metabolism
Peptide Fragments / genetics
Peptide Fragments / metabolism
Precipitin Tests
Proline
RNA, Messenger / analysis
Rabbits
Repetitive Sequences, Nucleic Acid
Subcellular Fractions / chemistry
Yeasts / genetics
src Homology Domains / genetics*

Substances

Adaptor Proteins, Signal Transducing
Carrier Proteins
HTT protein, human
Huntingtin Protein
Nerve Tissue Proteins
Nuclear Proteins
Peptide Fragments
RNA, Messenger
SH3GL3 protein, human
Glutamine
Proline