A positive feedback loop between Dumbfounded and Rolling pebbles leads to myotube enlargement in Drosophila.
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.
Menon
Sree Devi
SD
Temasek Lifesciences Laboratory, National University of Singapore, 1 Research Link, Singapore 117604. sreedevi@tll.org.sg
Osman
Zalina
Z
Chenchill
Kho
K
Chia
William
W
D000818:Animals; D019556:COS Cells; D002454:Cell Differentiation / Q000502:physiology; D002522:Chlorocebus aethiops; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D025461:Feedback, Physiological / Q000502:physiology; D007136:Immunoglobulins / Q000378:metabolism; D008561:Membrane Fusion / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000378:metabolism*; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology; D021381:Protein Transport / Q000502:physiology
D029721:Drosophila Proteins; D007136:Immunoglobulins; D008565:Membrane Proteins; D009124:Muscle Proteins; C410904:SNS protein, Drosophila; C413082:kirre protein, Drosophila; C443104:rols protein, Drosophila