Abstract
Caenorhabditis elegans C09F5.1 is a nematode-specific gene that encodes a type II transmembrane protein containing the BRICHOS domain. The gene was isolated as a heat-sensitive mutant, but the function of the protein remained unclear. We examined the expression pattern and subcellular localization of C09F5.1 as well as its roles in thermotolerance and chaperone function. Expression of C09F5.1 under heat shock conditions was induced in a heat shock factor 1 (HSF-1)–dependent manner. However, under normal growth conditions, most cells types exposed to mechanical stimuli expressed C09F5.1. Knockdown of C09F5.1 expression or deletion of the N-terminal domain decreased thermotolerance. The BRICHOS domain of C09F5.1 did not exhibit chaperone function unlike those of other proteins containing this domain, but the domain was essential for the proper subcellular localization of the protein. Intact C09F5.1 was localized to the Golgi body, but the N-terminal domain of C09F5.1 (C09F5.1-NTD) was retained in the ER. C09F5.1-NTD delayed paralysis by beta-amyloid (1-42) protein (Aβ42) in Alzheimer’s disease model worms (CL4176) and activated the unfolded protein response (UPR) by interacting with Aβ42. An intrinsically disordered region (IDR) located at the N-terminus of C09F5.1 may be responsible for the chaperone function of C09F5.1-NTD. Taken together, the data suggest that C09F5.1 triggers the UPR by interacting with abnormal proteins.
Highlights
Organisms recognize acute environmental changes such as high temperature, high salt, oxidizing conditions, or high levels of heavy metals as stress
C09F5.1 gene was isolated by differential-display reverse transcription–PCR
Because the C09F5.1-NTD interacts directly with Aβ42 and is localized in the endoplasmic reticulum (ER) and the directly with Aβ42 and is localized in the ER and the expression of C09F5.1-NTD reduced the rates of expression of C09F5.1-NTD reduced the rates of paralysis in these worms (Figure 5A), these findings paralysis in these worms (Figure 5A), these findings indicate that the complex of C09F5.1-NTD and indicate that the complex of C09F5.1-NTD and Aβ42 activated the unfolded protein response (UPR), which decreased the
Summary
Organisms recognize acute environmental changes such as high temperature, high salt, oxidizing conditions, or high levels of heavy metals as stress. Some environmental stresses cause denaturation of cellular proteins and accumulation of these denatured proteins is perceived as proteotoxic damage. To minimize this damage, the denatured proteins are degraded or refolded through the unfolded protein response (UPR) or endoplasmic reticulum–associated degradation (ERAD) pathway. Genes 2018, 9, 160 proteins (HSPs) are representative molecular chaperones induced by trimerization of heat shock transcription factor (HSF) following heat shock and other stresses [2,3,4]. Stress proteins can function as chaperones under normal conditions [5,6]. Chaperone proteins assist in proper folding of newly synthesized polypeptides into normal proteins or facilitate the transport of precursor polypeptide chains into appropriate subcellular organelles [7]. C09F5.1(ok2863) III hsf-1(sy441) I daf-16(mu86) I rrf-3(pk1426) II smg-1(cc546) I; rol-6(su1006) II smg-1(cc546) I; dvIs27 X b
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