SNED1 modulates ECM architecture and cell proliferation via its LDV integrin-binding motif.

The extracellular matrix (ECM) is a complex scaffold of proteins that supports multicellular organisms. Interactions between cells and the ECM via receptors, like integrins, govern cellular phenotypes (e.g. proliferation and adhesion), but also contribute to ECM assembly. Understanding how ECM-receptor interactions regulate matrix assembly is crucial to uncovering how alterations of the ECM cause or accompany congenital diseases, cancer or fibrosis. SNED1 is an understudied ECM protein with roles in development and metastasis. The mechanisms governing its assembly and signaling functions remain largely unknown. SNED1 contains two integrin-binding motifs, RGD and LDV, and we have recently shown that its interaction with RGD-integrins mediates cell adhesion. Here, we investigated the role of SNED1-integrin interactions in SNED1 ECM assembly. Although SNED1-integrin interactions were not necessary for the initial incorporation of SNED1 into the ECM, we found that the LDV motif, but not the RGE motif, in SNED1, was required for ECM build-up and the patterning of SNED1 and the fibrillar proteins fibronectin and collagen I. Moreover, the SNED1 LDV motif promoted ECM alignment, cell alignment and cell proliferation, processes essential to SNED1-driven neural crest cell migration during craniofacial development and breast cancer invasion.