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

Hiroshi Qadota, Annie McPherson, Rachel Corbitt, Evan Kelton Dackowski, Yohei Matsunaga, Andres F. Oberhauser, Guy M. Benian

Research output: Contribution to journalArticlepeer-review


Integrin plays a crucial role in the attachment of cells to the extracellular matrix. Integrin recruits many proteins intracellularly, including a 4-pro-tein 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.

Original languageEnglish (US)
Article numberjkac117
JournalG3: Genes, Genomes, Genetics
Issue number7
StatePublished - Jul 2022


  • KIPP complex
  • integrin
  • integrin adhesion complex
  • mutant screening
  • suppressor

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)


Dive into the research topics of 'Genetic analysis suggests a surface of PAT-4 (ILK) that interacts with UNC-112 (kindlin)'. Together they form a unique fingerprint.

Cite this