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A positive feedback loop between Dumbfounded and Rolling pebbles leads to myotube enlargement in Drosophila
Sree Devi Menon1, Zalina Osman, Kho Chenchill
1Temasek Lifesciences Laboratory, National University of Singapore, 1 Research Link, Singapore 117604. sreedevi@tll.org.sg
Abstract:
In Drosophila, myoblasts are subdivided into founders and fusion-competent myoblasts (fcm) with myotubes forming through fusion of one founder and several fcm. Duf and rolling pebbles 7 (Rols7; also known as antisocial) are expressed in founders, whereas sticks and stones (SNS) is present in fcm. Duf attracts fcm toward founders and also causes translocation of Rols7 from the cytoplasm to the fusion site. We show that Duf is a type 1 transmembrane protein that induces Rols7 translocation specifically when present intact and engaged in homophilic or Duf-SNS adhesion. Although its membrane-anchored extracellular domain functions as an attractant and is sufficient for the initial round of fusion, subsequent fusions require replenishment of Duf through cotranslocation with Rols7 tetratricopeptide repeat/coiled-coil domain-containing vesicles to the founder/myotube surface, causing both Duf and Rols7 to be at fusion sites between founders/myotubes and fcm. This implicates the Duf-Rols7 positive feedback loop to the occurrence of fusion at specific sites along the membrane and provides a mechanism by which the rate of fusion is controlled.
Insights
Duf attracts fusion-competent myoblasts (fcm) to founders and initiates myotube formation. A Duf-Rols7 feedback loop ensures sustained fusion by replenishing Duf at fusion sites.
Area of Science:
- Cell Biology
- Developmental Biology
- Genetics
Background:
- Myotube formation in Drosophila involves the fusion of founder myoblasts and fusion-competent myoblasts (fcm).
- Specific proteins, Duf and rolling pebbles 7 (Rols7), are expressed in founders, while sticks and stones (SNS) is in fcm.
- Duf attracts fcm and facilitates Rols7 translocation to fusion sites.
Purpose of the Study:
- To elucidate the mechanism by which Duf mediates myoblast fusion.
- To investigate the role of Duf-Rols7 interaction in sustained myotube formation.
- To understand how Duf and Rols7 regulate fusion site specificity and rate.
Main Methods:
- Utilized Drosophila as a model organism.
- Investigated the function of Duf as a type 1 transmembrane protein.
- Analyzed the translocation of Rols7 and its dependence on Duf engagement and vesicle-mediated replenishment.
Main Results:
- Duf induces Rols7 translocation when intact and engaged in homophilic or Duf-SNS adhesion.
- The extracellular domain of Duf is sufficient for initial fusion, acting as an attractant.
- Subsequent fusions require continuous Duf replenishment via Rols7-containing vesicles at the founder/myotube surface.
Conclusions:
- A Duf-Rols7 positive feedback loop is crucial for targeted myoblast fusion.
- This feedback mechanism controls the rate and specificity of myotube formation.
- Duf's cotranslocation with Rols7 vesicles ensures sustained fusion events.
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