title: Kon-tiki enhances PS2 integrin adhesion and localizes its ligand, Thrombospondin, in the myotendinous junction.
abstract: Cell-extracellular-matrix adhesion is mediated by cell receptors, mainly integrins and transmembrane proteoglycans, which can functionally interact. How these receptors are regulated and coordinated is largely unknown. We show that the conserved transmembraneDrosophilaproteoglycan Kon-tiki (Kon, also known as Perdido) interacts with the αPS2βPS integrin (αPS2 is encoded byinflatedand βPS bymyospheroid) to mediate muscle-tendon adhesion.konandinflateddouble mutant embryos show a synergistic increase in muscle detachment. Furthermore, Kon modulates αPS2βPS signaling at the muscle attachment, since phosphorylated Fak is reduced inkonmutants. This reduction in integrin signaling can be rescued by the expression of a truncated Kon protein containing its transmembrane and extracellular domains, suggesting that these domains are sufficient to mediate this signaling. We show that these domains are sufficient to properly localize the αPS2βPS ligand, Thrombospondin, to the muscle attachment, and to partially rescue Kon-dependent muscle-tendon adhesion. We propose that Kon can engage in a protein complex with αPS2βPS and enhance integrin-mediated signaling and adhesion by recruiting its ligand, which would increase integrin-binding affinity to the extracellular matrix, resulting in the consolidation of the myotendinous junction.
authors.affiliation: Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide/CSIC/JA, Seville 41013, Spain.
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Pérez-Moreno
authors.affiliation: Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide/CSIC/JA, Seville 41013, Spain.
authors.forename: Agueda G
authors.initials: AG
authors.lastname: Espina-Zambrano
authors.affiliation: Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide/CSIC/JA, Seville 41013, Spain.
authors.forename: Clara B
authors.initials: CB
authors.lastname: García-Calderón
authors.affiliation: Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide/CSIC/JA, Seville 41013, Spain bestmar@upo.es.
authors.forename: Beatriz
authors.identifier: 0000-0001-7833-5597
authors.initials: B
authors.lastname: Estrada
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002460:Cell Line; D029721:Drosophila Proteins / Q000737:chemistry / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000196:embryology / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000378:metabolism; D004843:Epistasis, Genetic; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D039001:Integrin alpha Chains / Q000378:metabolism*; D008024:Ligands; D009132:Muscles / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D000072417:Protein Domains; D021122:Protein Subunits / Q000378:metabolism; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D013710:Tendons / Q000378:metabolism*; D019699:Thrombospondins / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D039001:Integrin alpha Chains; D008024:Ligands; D009419:Nerve Tissue Proteins; D021122:Protein Subunits; D019699:Thrombospondins; C082188:if protein, Drosophila; C000619641:kon protein, Drosophila; D051416:Focal Adhesion Protein-Tyrosine Kinases
keywords: Adhesion; CSPG4; Chondroitin sulfate proteoglycan; Extracellular matrix; Integrin; Kon-tiki; Muscle; Myogenesis; Myotendinous junction; NG2; Perdido