Mind bomb 2, a founder myoblast-specific protein, regulates myoblast fusion and muscle stability

Abstract

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 fusioncompetent 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.

Muscle wasted: a novel component of theDrosophilahistone locus body required for muscle integrity

“…2L, arrow) and the embryos died prior to hatching (n200). These morphologies are characteristic of degenerating muscles (Carrasco-Rando and Ruiz-Gomez, 2008;Nguyen et al, 2007). These results demonstrate that mute loss of function results in progressive muscle degeneration late in embryonic development and that mute is required for maintenance of muscle integrity.…”

Jeb/Alk signalling regulates the Lame duck GLI family transcription factor in theDrosophilavisceral mesoderm

“…Recent analysis has identified genomic regions bound by Lmd that are also co-occupied by key regulators such as Twist, Tinman and Mef2 combinatorially regulating the expression of FCM-and FC-specific genes in the embryonic mesoderm (Busser et al, 2012). Interestingly, recent work indicates a role for the E3 ubiquitin ligase Mind bomb 2 (Mib2) in the regulation of Lmd protein levels (Carrasco-Rando and Ruiz-Gómez, 2008).…”

The E3 Ubiquitin Ligase Mind Bomb-2 (MIB2) Protein Controls B-cell CLL/Lymphoma 10 (BCL10)-dependent NF-κB Activation

“…So far, MIB2 has been associated with Notch and glutamate receptor signaling and was also shown to play a role in muscle stability in Drosophila (32)(33)(34). Although MIB2 was proposed as a potential candidate in a large scale analysis of human NF-B-inducing genes, its role in physiological signaling pathways remained undefined.…”

“…MIB2 has previously been associated with Notch and glutamate receptor signaling and was found to be involved in muscle stability in Drosophila (32)(33)(34). Its role in BCL10-dependent signaling and NF-B activation is unclear, even though MIB2 was previously identified as a potential NF-Binducing gene in a large scale screen for human NF-B-activating molecules (35).…”