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.

中文翻译：

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秀丽隐杆线虫 12-kDa 小热休克蛋白，在体外几乎没有伴侣活性，对其 dauer 形成、寿命和繁殖起着至关重要的作用

已知小热休克蛋白 (sHSP) 通过抑制错误折叠蛋白的聚集而表现出体外伴侣活性。然而，来自秀丽隐杆线虫的 12-kDa sHSP (Hsp12s) 亚家族成员，包括 Hsp12.2、Hsp12.3 和 Hsp12.6，缺乏这种伴侣活性，并且对其体内功能知之甚少。在这里，我们验证了 Hsp12.1，类似于其同源物 Hsp12.2、Hsp12.3 和 Hsp12.6，几乎没有表现出任何伴侣活性。引人注目的是，我们证明了这些 Hsp12 似乎在秀丽隐杆线虫中起着至关重要的生理作用，用于抑制 dauer 形成并促进长寿和繁殖。来自丝虫线虫Brugia malayi的独特sHSP基因被鉴定为编码两种产物，一种为全长Hsp12.6蛋白，另一种具有正常长度的N端臂但缺乏C端延伸。该基因可能代表从普通 sHSP 进化为 Hsp12 的中间形式。总之，我们的研究提供了关于伴侣缺陷型 sHSP 可能表现出的生物学功能的见解，并且还暗示了独特的 Hsp12s 亚家族的进化场景。