The Caenorhabditis elegans 12‐kDa small heat shock proteins with little in vitro chaperone activity play crucial roles for its dauer formation, longevity, and reproduction

Abstract

Small heat shock proteins (sHSPs) are known to exhibit in vitro chaperone activity by suppressing the aggregation of misfolded proteins. The 12-kDa sHSPs (Hsp12s) subfamily members from Caenorhabditis elegans, including Hsp12.2, Hsp12.3, and Hsp12.6, however, are devoid of such chaperone activity, and their in vivo functions are poorly understood. Here we verified that Hsp12.1, similar to its homologs Hsp12.2, Hsp12.3, and Hsp12.6, hardly exhibited any chaperone activity. Strikingly, we demonstrated that these Hsp12s seem to play crucial physiological roles in C. elegans, for suppressing dauer formation and promoting both longevity and reproduction. A unique sHSP gene from Filarial nematode worm Brugia malayi was identified such that it encodes two products, one as a full-length Hsp12.6 protein and the other one having an N-terminal arm of normal length but lacks the C-terminal extension. This gene may represent an intermediate form in evolution from a common sHSP to a Hsp12. Together, our study offers insights on what biological functions the chaperone-defective sHSPs may exhibit and also implicates an evolutionary scenario for the unique Hsp12s subfamily.

Global Host Responses to the Microbiota at Single Cell Resolution in Gnotobiotic Zebrafish

“…In a meta analysis of zebrafish proteins upregulated in response to various biological stressors, Cry proteins are among the top 25 protein families (Groh and J-F Suter, 2015). More broadly, small heat shock proteins similar to alpha crystallins are abundant in cells experiencing low metabolic states, such as in nematode dauers (Fu et al ., 2021) and brine shrimp and insects in diapause (King and Macrae, 2015; Khodajou-Masouleh et al ., 2021). Our global transcriptional analysis of GF cells suggests they are less proliferative and less metabolically active than CV counterparts, potentially necessitating cellular mechanisms to maintain cytoplasmic organization, prevent protein aggregation, and stabilize stalled, energetically costly processes, such as vesicular trafficking.…”

Cell-type-specific responses to the microbiota across all tissues of the larval zebrafish

“… 65 In a meta analysis of zebrafish proteins upregulated in response to various biological stressors, Cry proteins are among the top 25 protein families. 66 More broadly, small heat shock proteins similar to alpha crystallins are abundant in cells experiencing low metabolic states, such as in nematode dauers 67 and brine shrimp and insects in diapause. 68 , 69 Our global transcriptional analysis of GF cells within the Gnotobiotic Atlas suggests that they are less proliferative and less metabolically active than CVZ counterparts, potentially necessitating cellular mechanisms to maintain cytoplasmic organization, prevent protein aggregation, and stabilize stalled, energetically costly processes, such as vesicular trafficking.…”

The major inducible small heat shock protein HSP20-3 in the tardigrade Ramazzottius varieornatus forms filament-like structures and is an active chaperone

“…In the nematode, Caenorhabditis elegans , there are 16 sHSPs expressed 7 , 86 with similar variability in their structure-function properties 87 . The HSP-12 class of sHSPs within C.elegans are critical for dauer formation, longevity and fecundity 88 , but these proteins do not oligomerise and show poor in vitro chaperone activity 88 , 89 . By contrast, most of the HSP-16 class of sHSPs, do oligomerise and have classical chaperone properties shown by in vitro chaperone assays 87 , 90 .…”