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Thrombospondin-4 controls matrix assembly during development and repair of myotendinous junctions

Tendons are extracellular matrix (ECM)-rich structures that mediate muscle attachments with the skeleton, but surprisingly little is known about molecular mechanisms of attachment. Individual myofibers and tenocytes in Drosophila interact through integrin (Itg) ligands such as Thrombospondin (Tsp),...

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Detalles Bibliográficos
Autores principales: Subramanian, Arul, Schilling, Thomas F
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4096842/
https://www.ncbi.nlm.nih.gov/pubmed/24941943
http://dx.doi.org/10.7554/eLife.02372
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author Subramanian, Arul
Schilling, Thomas F
author_facet Subramanian, Arul
Schilling, Thomas F
author_sort Subramanian, Arul
collection PubMed
description Tendons are extracellular matrix (ECM)-rich structures that mediate muscle attachments with the skeleton, but surprisingly little is known about molecular mechanisms of attachment. Individual myofibers and tenocytes in Drosophila interact through integrin (Itg) ligands such as Thrombospondin (Tsp), while vertebrate muscles attach to complex ECM fibrils embedded with tenocytes. We show for the first time that a vertebrate thrombospondin, Tsp4b, is essential for muscle attachment and ECM assembly at myotendinous junctions (MTJs). Tsp4b depletion in zebrafish causes muscle detachment upon contraction due to defects in laminin localization and reduced Itg signaling at MTJs. Mutation of its oligomerization domain renders Tsp4b unable to rescue these defects, demonstrating that pentamerization is required for ECM assembly. Furthermore, injected human TSP4 localizes to zebrafish MTJs and rescues muscle detachment and ECM assembly in Tsp4b-deficient embryos. Thus Tsp4 functions as an ECM scaffold at MTJs, with potential therapeutic uses in tendon strengthening and repair. DOI: http://dx.doi.org/10.7554/eLife.02372.001
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spelling pubmed-40968422014-07-22 Thrombospondin-4 controls matrix assembly during development and repair of myotendinous junctions Subramanian, Arul Schilling, Thomas F eLife Cell Biology Tendons are extracellular matrix (ECM)-rich structures that mediate muscle attachments with the skeleton, but surprisingly little is known about molecular mechanisms of attachment. Individual myofibers and tenocytes in Drosophila interact through integrin (Itg) ligands such as Thrombospondin (Tsp), while vertebrate muscles attach to complex ECM fibrils embedded with tenocytes. We show for the first time that a vertebrate thrombospondin, Tsp4b, is essential for muscle attachment and ECM assembly at myotendinous junctions (MTJs). Tsp4b depletion in zebrafish causes muscle detachment upon contraction due to defects in laminin localization and reduced Itg signaling at MTJs. Mutation of its oligomerization domain renders Tsp4b unable to rescue these defects, demonstrating that pentamerization is required for ECM assembly. Furthermore, injected human TSP4 localizes to zebrafish MTJs and rescues muscle detachment and ECM assembly in Tsp4b-deficient embryos. Thus Tsp4 functions as an ECM scaffold at MTJs, with potential therapeutic uses in tendon strengthening and repair. DOI: http://dx.doi.org/10.7554/eLife.02372.001 eLife Sciences Publications, Ltd 2014-06-18 /pmc/articles/PMC4096842/ /pubmed/24941943 http://dx.doi.org/10.7554/eLife.02372 Text en Copyright © 2014, Subramanian and Schilling http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Cell Biology
Subramanian, Arul
Schilling, Thomas F
Thrombospondin-4 controls matrix assembly during development and repair of myotendinous junctions
title Thrombospondin-4 controls matrix assembly during development and repair of myotendinous junctions
title_full Thrombospondin-4 controls matrix assembly during development and repair of myotendinous junctions
title_fullStr Thrombospondin-4 controls matrix assembly during development and repair of myotendinous junctions
title_full_unstemmed Thrombospondin-4 controls matrix assembly during development and repair of myotendinous junctions
title_short Thrombospondin-4 controls matrix assembly during development and repair of myotendinous junctions
title_sort thrombospondin-4 controls matrix assembly during development and repair of myotendinous junctions
topic Cell Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4096842/
https://www.ncbi.nlm.nih.gov/pubmed/24941943
http://dx.doi.org/10.7554/eLife.02372
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