A new mouse mutant with cleavage-resistant versican and isoform-specific versican mutants demonstrate that proteolysis at the Glu⁴⁴¹-Ala⁴⁴² peptide bond in the V1 isoform is essential for interdigital web regression.

ABSTRACT: Two inherent challenges in the mechanistic interpretation of protease-deficient phenotypes are defining the specific substrate cleavages whose reduction generates the phenotypes and determining whether the phenotypes result from loss of substrate function, substrate accumulation, or loss of a function(s) embodied in the substrate fragments. Hence, recapitulation of a protease-deficient phenotype by a cleavage-resistant substrate would stringently validate the importance of a proteolytic event and clarify the underlying mechanisms. Versican is a large proteoglycan required for development of the circulatory system and proper limb development, and is cleaved by ADAMTS proteases at the Glu⁴⁴¹-Ala⁴⁴² peptide bond located in its alternatively spliced GAGβ domain. Specific

SUBMITTER: Nandadasa S 

PROVIDER: S-EPMC8233476 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature