title: LINKIN, a new transmembrane protein necessary for cell adhesion.
abstract: In epithelial collective migration, leader and follower cells migrate while maintaining cell-cell adhesion and tissue polarity. We have identified a conserved protein and interactors required for maintaining cell adhesion during a simple collective migration in the developing C. elegans male gonad. LINKIN is a previously uncharacterized, transmembrane protein conserved throughout Metazoa. We identified seven atypical FG-GAP domains in the extracellular domain, which potentially folds into a β-propeller structure resembling the α-integrin ligand-binding domain. C. elegans LNKN-1 localizes to the plasma membrane of all gonadal cells, with apical and lateral bias. We identified the LINKIN interactors RUVBL1, RUVBL2, and α-tubulin by using SILAC mass spectrometry on human HEK 293T cells and testing candidates for lnkn-1-like function in C. elegans male gonad. We propose that LINKIN promotes adhesion between neighboring cells through its extracellular domain and regulates microtubule dynamics through RUVBL proteins at its intracellular domain.
authors.affiliation: Division of Biology and Biological Engineering, Howard Hughes Medical Institute, California Institute of Technology, Pasadena, United States.
authors.forename: Mihoko
authors.initials: M
authors.lastname: Kato
authors.affiliation: Division of Biology and Biological Engineering, Howard Hughes Medical Institute, California Institute of Technology, Pasadena, United States.
authors.forename: Tsui-Fen
authors.initials: TF
authors.lastname: Chou
authors.affiliation: Division of Biology and Biological Engineering, Howard Hughes Medical Institute, California Institute of Technology, Pasadena, United States.
authors.forename: Collin Z
authors.initials: CZ
authors.lastname: Yu
authors.affiliation: Division of Biology and Biological Engineering, Howard Hughes Medical Institute, California Institute of Technology, Pasadena, United States.
authors.forename: John
authors.initials: J
authors.lastname: DeModena
authors.affiliation: Division of Biology and Biological Engineering, Howard Hughes Medical Institute, California Institute of Technology, Pasadena, United States.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Sternberg
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000378:metabolism*; D002448:Cell Adhesion; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement; D017124:Conserved Sequence; D017353:Gene Deletion; D017238:Genes, Helminth; D006066:Gonads / Q000166:cytology; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008938:Mitosis; D008954:Models, Biological; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D034622:RNA Interference
chemical_list: D029742:Caenorhabditis elegans Proteins; D008565:Membrane Proteins; C000600215:lnkn-1 protein, C elegans
keywords: C. elegans; cell biology; cell migration; cell polarity; developmental biology; human cells; organogenesis; protein–protein interactions; stem cells