C. elegans STI-1, homolog of Sti1/Hop, is involved in ageing and stress response

Abstract

Environmental and physiological stresses such as heat shock, oxidative stress, heavy metals and pathogenic conditions induce the cellular stress response. This response is often related to the heat shock proteins (HSPs) that function as molecular chaperones or proteases. A stress-inducible co-chaperone, Sti1/Hop (Hsp organizer protein), functions as an adaptor protein that can bind to Hsp90 and Hsp70 simultaneously to transfer client proteins from Hsp70 to Hsp90. However, the biological role of STI1 in vivo is poorly understood. Here, we report C. elegans homolog of STI1/Hop, sti-1, which is approximately 56% identical to human STI1. Using C. elegans, we characterize the in vivo function of STI-1 related to stress conditions. The CeSTI-1 is expressed in pharynx, intestine, nervous system and male tail from larva to adult. The isolated sti-1(jh125) deletion mutant shows small brood size and short life span under heat stress condition. In addition, sti-1 expression is elevated by heat stress. Our results suggest that CeSTI-1 is required for regulation of longevity and stress response, especially heat stress. Coimmunoprecipitation and following MS/MS analysis uncovers that CeSTI-1 can bind to its binding partners, Hsp90 and Hsp70 as like mammal. This suggests that molecular function of STI-1 is well conserved in C. elegans. 67