Tan, Chieh-Hsiang and Cheng, Kai-Wen and Park, Heenam and Sternberg, Paul W. and Chou, Tsui-Fen (2023) LINKIN-associated proteins necessary for tissue integrity during collective cell migration. . (Unpublished) https://resolver.caltech.edu/CaltechAUTHORS:20230316-182235000.22
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Abstract
Cell adhesion plays essential roles in almost every aspect of metazoan biology. Previously, using the developmental migration of the nematode male gonad as a platform, LINKIN (Human: ITFG1,C. elegans: lnkn-1), a relatively understudied transmembrane protein conserved across the metazoa, was found to be necessary for tissue integrity during migration. InC. elegans, loss of lnkn-1 results in the detachment of the lead migratory cell from the rest of the developing male gonad. Three interactors of ITFG1/lnkn-1-RUVBL1/ruvb-1, RUVBL2/ruvb-2, and alpha-tubulin were identified by proteomic analysis using the human HEK293T cells and 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. In this study, we showed that epitope-tagged ITFG1 localized to the cell surface of MDA-MB-231 breast cancer cells. Using unbiased mass spectrometry-based proteomics, 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 the same as LINKIN (notably cohesion and condensin) suggests the involvement of membrane remodeling and chromosome biology in the tight adhesion dependent on LINKIN, and support the hypothesis for a structure role of chromosomes in post-mitotic cells.
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| Additional Information: | The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. We thank Barbara Perry, Wilber Palma and Stephanie Nava for laboratory assistance. We thank members of our laboratory for discussions. Mutant alleles- mvk-1(tm6628), trd-1(tm2764), vha-19(tm2225), prx-3(tm6469), and rod-1(tm6186) were provided by the MITANI Lab through the National Bio-Resource Project of the MEXT, Japan. Some strains were obtained from the Caenorhabditis Genetics Center (CGC), which is funded by the NIH Office of Research Infrastructure Programs (P40 OD010440). This work was also facilitated by WormBase, a knowledgebase for nematode research; and by the Alliance of Genome Resources, a research platform that facilitates cross species research, This research was supported by NIH R01HD086596 (PWS and TFC), R01HD091327 (PWS), and R24 0D023041 (PWS). The authors have declared no competing interest. | ||||||||||||
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| DOI: | 10.1101/2023.02.08.527750 | ||||||||||||
| Record Number: | CaltechAUTHORS:20230316-182235000.22 | ||||||||||||
| Persistent URL: | https://resolver.caltech.edu/CaltechAUTHORS:20230316-182235000.22 | ||||||||||||
| Usage Policy: | No commercial reproduction, distribution, display or performance rights in this work are provided. | ||||||||||||
| ID Code: | 120139 | ||||||||||||
| Collection: | CaltechAUTHORS | ||||||||||||
| Deposited By: | George Porter | ||||||||||||
| Deposited On: | 21 Mar 2023 20:01 | ||||||||||||
| Last Modified: | 21 Mar 2023 20:01 |
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