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Projekt
Dynamic remodelling of the muscle-tendon cell contact in Drosophila
Antragsteller
Dr. Frank Schnorrer
Fachliche Zuordnung
Entwicklungsbiologie
Förderung
Förderung von 2014 bis 2017
Projektkennung
Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 200509276
Precise coordination of muscle-tendon attachment and myofibrillogenesis is important to form a stable muscle-tendon contact. Without proper coordination premature muscle contractions would destroy an unstable muscle-tendon junction and lead to severe myopathies. By studying the temporal dynamics of muscle-tendon contact formation in Drosophila flight muscle we found that attachment begins as a dynamic cell-cell contact between tendon cells and myotubes, which is mediated by the orphan transmembrane receptor Kon-tiki (Kon). Kon is required in the muscle to mediate cell-cell recognition of the tendons and is concentrated at muscle-tendon contact. This is initial muscle-tendon contact is devoid of ECM, which is only recruited during attachment maturation, to form a stable force-resistant muscle-tendon junction. We found that this remodelling coincides with the formation of mechanical tension within the myotendinous system before simultaneous myofibrillogenesis is triggered in the muscle. In Aim 1 of this proposal we plan to investigate the mechanism how kon mediates attachment initiation. We will investigate the impact of kon removal on the actin and microtubule cytoskeleton. Moreover, we will explore potential links of Kon to Cadherin, which also localises to the muscle-tendon contact. In Aim 2 we will study the contribution of the microtubule cytoskeleton to remodelling of the myotendinous interface and the formation of tension. A combination of functional RNAi data with direct microtubule manipulations should identify important microtubule associated proteins that participate in these processes. In Aim 3 we intend to test the spectraplakin homolog Shortstop (Shot) a role for in attachment and tension formation. Shot is found concentrated at the myotendinous interface and can bind to both microtubules and actin filaments. Thus, Shot may link attachment and the formation of tension to myofibrillogenesis. Together, these experiments should lead to a better understanding of how the remodelling of the muscle-tendon interface from dynamic cell-cell contacts to a stable junction allows formation of tension and can eventually trigger myofibrillogenesis.
DFG-Verfahren
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