PUBLICATION
Thrombospondin-4 controls matrix assembly during development and repair of myotendinous junctions
- Authors
- Subramanian, A., Schilling, T.F.
- ID
- ZDB-PUB-140620-9
- Date
- 2014
- Source
- eLIFE 6(8): e02372 (Journal)
- Registered Authors
- Schilling, Tom, Subramanian, Arul
- Keywords
- Zebrafish, ECM organization, muscle attachment, myotendinous junctions, tendon development
- MeSH Terms
-
- Animals
- Extracellular Matrix/metabolism*
- Humans
- Integrins/metabolism
- Ligands
- Microscopy, Electron, Transmission
- Muscles/metabolism
- Mutation
- Protein Binding
- Protein Conformation
- Signal Transduction
- Tendons/pathology*
- Tendons/physiology*
- Thrombospondins/physiology*
- Zebrafish
- PubMed
- 24941943 Full text @ Elife
Citation
Subramanian, A., Schilling, T.F. (2014) Thrombospondin-4 controls matrix assembly during development and repair of myotendinous junctions. eLIFE. 6(8):e02372.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping