From the Department of Biochemistry and Molecular Biology, Oregon Health and Science University, Portland, Oregon 97239.
the Research Department, Shriners Hospital for Children, Portland, Oregon 97239, and.
J Biol Chem. 2018 Aug 31;293(35):13707-13716. doi: 10.1074/jbc.RA117.000758. Epub 2018 Jul 12.
The build-up of diversified and tissue-specific assemblies of extracellular matrix (ECM) proteins depends on secreted and cell surface-located molecular arrays that coordinate ECM proteins into discrete designs. The family of small leucine-rich proteins (SLRPs) associates with and dictates the structure of fibrillar collagens, which form the backbone of most ECM types. However, whether SLRPs form complexes with proteins other than collagens is unclear. Here, we demonstrate that heat shock protein 47 (Hsp47), a well-established endoplasmic reticulum-resident collagen chaperone, also binds the SLRPs decorin, lumican, and fibromodulin with affinities comparable with that in the Hsp47-type I collagen interaction. Furthermore, we show that a lack of Hsp47 inhibits the cellular secretion of decorin and lumican. Our results expand the understanding of the concerted molecular interactions that control the secretion and organization of a functional collagenous ECM.
细胞外基质（ECM）蛋白的多样化和组织特异性组装取决于分泌的和位于细胞表面的分子阵列，这些分子阵列将 ECM 蛋白协调成离散的设计。小富含亮氨酸的蛋白（SLRPs）家族与纤维胶原结合，并决定其结构，而纤维胶原构成大多数 ECM 类型的骨干。然而，SLRPs 是否与除胶原蛋白以外的蛋白质形成复合物尚不清楚。在这里，我们证明热休克蛋白 47（Hsp47），一种公认的内质网驻留胶原蛋白伴侣，也与 SLRPs 核心蛋白聚糖、lumican 和 fibromodulin 结合，亲和力与 Hsp47-Ⅰ型胶原蛋白相互作用相当。此外，我们还表明 Hsp47 的缺乏抑制了核心蛋白聚糖和 lumican 的细胞分泌。我们的结果扩展了对控制功能性胶原 ECM 分泌和组织的协同分子相互作用的理解。
