[
Proc Natl Acad Sci U S A,
2002]
Communicated by William B. Wood, University of Colorado, Boulder, CO, May 24, 2002 (received for review March 22, 2002) Expression of the human ss amyloid peptide (Ass) in transgenic Caenorhabditis elegans animals can lead to the formation of intracellular immunoreactive deposits as well as the formation of intracellular amyloid. We have used this model to identify proteins that interact with intracellular Ass in vivo. Mass spectrometry analysis of proteins that specifically coimmunoprecipitate with Ass has identified six likely chaperone proteins: two members of the HSP70 family, three alphaB-crystallin-related small heat shock proteins (HSP-16s), and a putative ortholog of a mammalian small glutamine-rich tetratricopeptide repeat-containing protein proposed to regulate HSP70 function. Quantitative reverse transcription--PCR analysis shows that the small heat shock proteins are also transcriptionally induced by Ass expression. Immunohistochemistry demonstrates that HSP-16 protein closely colocalizes with intracellular Ass in this model. Transgenic animals expressing a nonaggregating Ass variant, a single-chain Ass dimer, show an altered pattern of coimmunoprecipitating proteins and an altered cellular distribution of HSP-16. Double-stranded RNA inhibition of R05F9.10, the putative C. elegans ortholog of the human small glutamine-rich tetratricopeptide-repeat-containing protein (SGT), results in suppression of toxicity associated with Ass expression. These results suggest that chaperone function can play a role in modulating intracellular Ass metabolism and toxicity.