Abstract
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.
Highlights
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 Extracellular matrices (ECMs) proteins into discrete designs
We demonstrate that heat shock protein 47 (Hsp47), a well-established endoplasmic reticulum– resident collagen chaperone, binds the small leucine-rich proteins (SLRPs) decorin, lumican, and fibromodulin with affinities comparable with that in the Hsp47–type I collagen interaction
Hsp47 interacts with SLRPs incubated with biotinylated recombinant decorin, fibromodulin, or lumican
Summary
The endoplasmic reticulum–resident collagen chaperone Hsp interacts with and promotes the secretion of decorin, fibromodulin, and lumican. 3 The abbreviations used are: ECM, extracellular matrix; ER, endoplasmic reticulum; rER, rough endoplasmic reticulum; SLRP, small leucine-rich protein; SPR, surface plasmon resonance; SH3, Src homology 3; PLA, proximity ligation assay; RU, reference units; DMEM, Dulbecco’s modified Eagle’s medium; BisTris, 2-[bis(2-hydroxyethyl)amino]-2-(hydroxymethyl)propane-1,3diol; DCN, decorin; FM, fibromodulin; LUM, lumican; HRP, horseradish peroxidase. We investigated whether the collagen-associated SLRPs decorin [29, 30], lumican [31, 32], and fibromodulin [33, 34] could interact with any intracellular collagen–associated proteins and, if so, what the consequences of these interactions might be
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