Although collagens are the most abundant proteins implicated in various disease pathways, essential mechanisms required for their proper folding and assembly are poorly understood. Heat‐shock protein 47 (HSP47), an ER‐resident chaperone, was mainly reported to fulfill key functions in folding and secretion of fibrillar collagens by stabilizing pro‐collagen triple‐helices. In this study, we demonstrate unique functions of HSP47 for different collagen subfamilies. Our results show that HSP47 binds to the N‐terminal region of procollagen I and is essential for its secretion. However, HSP47 ablation does not majorly impact collagen VI secretion, but its lateral assembly. Moreover, specific ablation of Hsp47 in murine keratinocytes revealed a new role for the transmembrane collagen XVII triple‐helix formation. Incompletely folded collagen XVII C‐termini protruding from isolated HSP47 null keratinocyte membrane vesicles could be fully restored upon the application of recombinant HSP47. Thus, our study expands the current view regarding the client repertoire and function of HSP47, as well as emphasizes its importance for transmembrane collagen folding.

中文翻译：

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新的特定 HSP47 在胶原蛋白亚家族伴侣中的功能

尽管胶原蛋白是与各种疾病途径有关的最丰富的蛋白质，但对其正确折叠和组装所需的基本机制知之甚少。据报道，热休克蛋白 47 (HSP47) 是一种内质网驻留分子伴侣，主要通过稳定前胶原三螺旋来实现纤维状胶原折叠和分泌的关键功能。在这项研究中，我们展示了 HSP47 对不同胶原亚家族的独特功能。我们的结果表明 HSP47 与原胶原 I 的 N 端区域结合，对其分泌至关重要。然而，HSP47 消融不会主要影响胶原蛋白 VI 的分泌，但会影响其横向组装。此外，小鼠角质形成细胞中 Hsp47 的特异性消融揭示了跨膜胶原蛋白 XVII 三螺旋形成的新作用。在应用重组 HSP47 后，从分离的 HSP47 无效角质形成细胞膜囊泡中突出的不完全折叠的胶原蛋白 XVII C 端可以完全恢复。因此，我们的研究扩展了目前关于 HSP47 的客户库和功能的观点，并强调了其对跨膜胶原蛋白折叠的重要性。