Mind bomb 2, a founder myoblast-specific protein, regulates myoblast fusion and muscle stability
2008
A fundamental step during Drosophila myogenesis is the
specification of founder myoblasts (FMs). Founders possess the information
required for the acquisition of muscle identity and for the execution of the
myogenic programme, whereas fusion-competent myoblasts (FCMs) acquire this
information after fusing to founders. Very little is known about genes that
implement the execution of the myogenic programme. Here we characterise Mind
bomb 2 (Mib2), a protein with putative E3 ubiquitin ligase activity that is
exclusive of FMs and necessary for at least two distinct steps of the
founder/myotube differentiation programme. Thus, in mib2 mutants, the
early process of myoblast fusion is compromised, as FMs undergo a reduced
number of rounds of fusion with FCMs. At later stages, with the onset of
muscle contraction, many muscles degenerate, display aberrant sarcomeric
structure and detach from tendons. The fusion process requires intact
E3-RING-finger domains of Mib2 (the putative catalytic sites), probably to
eliminate the FCM-specific activator Lmd from nascent myotubes. However, these
sites appear dispensable for muscle integrity. This, and the subcellular
accumulation of Mib2 in Z and M bands of sarcomeres, plus its physical
interaction with nonmuscle myosin (a Z-band-localised protein necessary for
the formation of myofibrils), suggest a structural role for Mib2 in
maintaining sarcomeric stability. We suggest that Mib2 acts sequentially in
myoblast fusion and sarcomeric stability by two separable processes involving
distinct functions of Mib2.
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