Cycles of muscle fusion

One round of fusion begets another, according to Menon et al. (page 909). This positive feedback keeps muscle formation going in the developing fly.Multinucleated muscles are a product of the fusion between one founder cell, which expresses the attractant Duf, and fusion-competent myoblasts (fcms) that produce the Duf ligand. Although as many as 25 myoblasts eventually become one, the founder only fuses with two or three fcms at a time. The new results reveal the basis for this sequence: one round of fusion consumes the founder's surface-bound Duf, but then triggers the translocation of more Duf from intracellular stores.

Translocation was initiated by adhesion of Duf's extracellular domain to an fcm ligand. The intracellular domain of the adhered Duf then transmitted an unknown signal that recruited puncta (probably endosomes) containing more Duf to the adhesion site. This Duf was then inserted into the membrane to attract a new fcm to the same spot where the previous fcm fused.

Duf translocation requires another puncta-localized protein called Rols7. In the absence of Rols7, only one round of fusion was possible, as Duf was not replenished. Rols7 must have an additional function during fusion, since a mutant that was missing multiple domains translocated effectively but did not support multiple rounds of fusion.