SH3GL3 Associates with the Huntingtin Exon 1 Protein and Promotes the Formation of Polygln-Containing Protein Aggregates
| Autor: | Erich E. Wanker, Renate Hasenbank, Eberhard Scherzinger, Holger Eickhoff, Hans Lehrach, Niels Wedemeyer, Stephanie Wälter, Annie Sittler, Gillian P. Bates |
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| Rok vydání: | 1998 |
| Předmět: |
Huntingtin
Proline Glutamine Gene Expression Nerve Tissue Proteins Protein aggregation Biology SH3 domain src Homology Domains Yeasts medicine Huntingtin Protein Animals Humans RNA Messenger Molecular Biology Adaptor Proteins Signal Transducing Repetitive Sequences Nucleic Acid Brain Chemistry COS cells Neurodegeneration Nuclear Proteins Signal transducing adaptor protein Colocalization Exons Cell Biology medicine.disease Precipitin Tests Molecular biology Peptide Fragments Huntington Disease COS Cells Rabbits Carrier Proteins Subcellular Fractions |
| Zdroj: | Molecular Cell. 2:427-436 |
| ISSN: | 1097-2765 |
| DOI: | 10.1016/s1097-2765(00)80142-2 |
| Popis: | The mechanism by which aggregated polyglns 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. |
| Databáze: | OpenAIRE |
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