Missense mutation of a conserved residue in UNC-112 (kindlin) eliminates binding to PAT-4 (ILK).

• Type of Material: Article
• Authors: Hiroshi Qadota, Emory University; Andres F Oberhauser, University of Texas Medical Branch, Galveston, Texas.; Guy Benian, Emory University
• Language: English
• Date: 2021
• Publisher: microPublication Biology
• Publication Version: Final Published Version
• Copyright Statement: © 2021 by the authors
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.17912/micropub.biology.000454
• Title of Journal or Parent Work: MicroPubl Biol
• Volume: 2021
• Grant/Funding Information: This study was supported by a previous grant from the American Heart Association (11GRNT7820000).
• Keywords: Missense mutation
• Research Categories: Health Sciences, Pathology

Abstract

C. elegans UNC-112 (kindlin) is required for muscle sarcomere assembly, and is one component of a conserved four-protein complex that associates with the cytoplasmic tail of integrin at the base of integrin adhesion complexes in muscle. The four-protein complex consists of UNC-112 (kindlin), PAT-4 (integrin linked kinase; ILK), PAT-6 (alpha-parvin), and UNC-97 (PINCH). UNC-112 is comprised of 720 amino acid residues and contains FERM and PH domains. The N-terminal half of UNC-112 (1-396 aa) can bind to the C-terminal half of UNC-112 (397-720 aa), and this interaction is inhibited by the association of PAT-4 (ILK) to the N-terminal half of UNC-112. In support of this model, previously, we reported identification of a D382V mutation that results in lack of binding to PAT-4. However, this residue is not conserved in human Kindlins. Here, we report identification of a novel UNC-112 mutation of a conserved residue that cannot bind to PAT-4. UNC-112 E302G cannot bind to PAT-4 and does not localize to integrin adhesion complexes in muscle.