Functional Analysis of p.Ala253_Leu254insAsn Mutation in PLS3 Responsible for X-linked Osteoporosis.

Functional Analysis of p.Ala253_Leu254insAsn Mutation in PLS3 Responsible for X-linked Osteoporosis. Clin Genet. 2017 Jun 24;: Authors: Wang L, Zhai Q, Zhao P, Xiang X, Zhang X, Tian W, Li T Abstract Mutations in Plastin-3 (PLS3) have been identified as a cause of X-linked osteoporosis. To reveal the molecular mechanism of PLS3 on osteoporosis, we characterized the p.Ala253_Leu254insAsn mutation in PLS3. We first identified Lymphocyte cytosolic protein 1 (LCP1) as a binding partner of PLS3 and the mutation disrupted the interaction between them. We then confirmed the roles of PLS3 and LCP1 in the regulation of intracellular Ca(2+) , which was weakened by the mutant PLS3. Moreover, the interaction between PLS3 and LCP1 was enhanced under a low concentration of extracellular Ca(2+) . However, the mutation in PLS3 weakened the responsiveness. The reduced regulation on Ca(2+) caused by p.Ala253_Leu254insAsn may be the possible molecular mechanism of osteoporosis. PMID: 28646489 [PubMed - as supplied by publisher]
Source: Clinical Genetics - Category: Genetics & Stem Cells Authors: Tags: Clin Genet Source Type: research