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Published online 13 June 2005. doi:10.1083/jcb.200501126
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 169, Number 6, 909-920
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Article

 A positive feedback loop between Dumbfounded and Rolling pebbles leads to myotube enlargement in Drosophila

Sree Devi Menon1, Zalina Osman1, Kho Chenchill1, and William Chia1,2

1 Temasek Lifesciences Laboratory, National University of Singapore, 1 Research Link, Singapore 117604
2 Centre for Developmental Neurobiology, King's College London, Guy's Hospital, London SE1 1UL, England, UK

Correspondence to Sree Devi Menon: sreedevi{at}tll.org.sg; or William Chia: william.chia{at}kcl.ac.uk

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.

Abbreviations used in this paper: blow, blownfuse; D-mef2, Drosophila-myocyte enhancer factor 2; duf, dumbfounded; EC, extracellular; Eve, Even-skipped; fcm, fusion-competent myoblasts; hbs, hibris; IC, intracellular; lmd, lame duck; mbc, myoblast city; rols7, rolling pebbles 7; rst, roughest; sns, sticks and stones; TM, transmembrane; TPR, tetratricopeptide repeat; WT, wild-type.


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