LINKIN-associated proteins necessary for tissue integrity during collective cell migration
bioRxiv the preprint server for biology(2023)
Abstract
Cell adhesion plays essential roles in almost every aspect of metazoan biology. LINKIN (Human: ITFG1, Caenorhabditis elegans : lnkn-1 ) is a conserved transmembrane protein that has been identified to be necessary for tissue integrity during migration. In C. elegans , loss of lnkn-1 results in the detachment of the lead migratory cell from the rest of the developing male gonad. Previously, three interactors of ITFG1/ lnkn-1 – RUVBL1/ ruvb-1 , RUVBL2/ ruvb-2 , and alpha-tubulin – were identified by immunoprecipitation-mass spectrometry (IP-MS) analysis using human HEK293T cells and then validated in the nematode male gonad. The ITFG1-RUVBL1 interaction has since been independently validated in a breast cancer cell line model that also implicates the involvement of the pair in metastasis. Here, we showed that epitope-tagged ITFG1 localized to the cell surface of MDA-MB-231 breast cancer cells. Using IP-MS analysis, we identified a new list of potential interactors of ITFG1. Loss-of-function analysis of their C. elegans orthologs found that three of the interactors – ATP9A/ tat-5 , NME1/ ndk-1 , and ANAPC2/ apc-2 – displayed migratory detachment phenotypes similar to that of lnkn-1 . Taken together with the other genes whose reduction-of-function phenotype is similar to that of lnkn-1 (notably cohesion and condensin), suggests the involvement of membrane remodeling and chromosome biology in LINKIN-dependent cell adhesion and supports the hypothesis for a structural role of chromosomes in post-mitotic cells.
### Competing Interest Statement
The authors have declared no competing interest.
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Key words
Kinesin Proteins
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