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Genetic analysis suggests a surface of PAT-4 (ILK) that interacts with UNC-112 (kindlin).

Authors :
Hiroshi Qadota
McPherson, Annie
Corbitt, Rachel
Dackowski, Evan Kelton
Yohei Matsunaga
Oberhauser, Andres F.
Benian, Guy M.
Source :
G3: Genes | Genomes | Genetics. Jul2022, Vol. 12 Issue 7, p1-11. 11p.
Publication Year :
2022

Abstract

Integrin plays a crucial role in the attachment of cells to the extracellular matrix. Integrin recruits many proteins intracellularly, including a 4-protein complex (kindlin, ILK, PINCH, and parvin). Caenorhabditis elegans muscle provides an excellent model to study integrin adhesion complexes. In Caenorhabditis elegans, UNC-112 (kindlin) binds to the cytoplasmic tail of PAT-3 (b-integrin) and to PAT-4 (ILK). We previously reported that PAT-4 binding to UNC-112 is essential for the binding of UNC-112 to PAT-3. Although there are crystal structures for ILK and a kindlin, there is no co-crystal structure available. To understand the molecular interaction between PAT-4 and UNC-112, we took a genetic approach. First, using a yeast 2-hybrid method, we isolated mutant PAT-4 proteins that cannot bind to UNC-112 and then isolated suppressor mutant UNC-112 proteins that restore interaction with mutant PAT-4 proteins. Second, we demonstrated that these mutant PAT-4 proteins cannot localize to attachment structures in nematode muscle, but upon co-expression of an UNC-112 suppressor mutant protein, mutant PAT- 4 proteins could localize to attachment structures. Third, overexpression of a PAT-4 mutant results in the disorganization of adhesion plaques at muscle cell boundaries and co-expression of the UNC-112 suppressor mutant protein alleviates this defect. Thus, we demonstrate that UNC-112 binding to PAT-4 is required for the localization and function of PAT-4 in integrin adhesion complexes in vivo. The missense mutations were mapped onto homology models of PAT-4 and UNC-112, and taking into account previously isolated mutations, we suggest a surface of PAT-4 that binds to UNC-112. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
21601836
Volume :
12
Issue :
7
Database :
Academic Search Index
Journal :
G3: Genes | Genomes | Genetics
Publication Type :
Academic Journal
Accession number :
157862539
Full Text :
https://doi.org/10.1093/g3journal/jkac117