Drosophila mind bomb2is required for maintaining muscle integrity and survival

Abstract

We report that the Drosophila mind bomb2 (mib2) gene is a novel regulator of muscle development. Unlike its paralogue, mib1, zygotic expression of mib2 is restricted to somatic and visceral muscle progenitors, and their respective differentiated musculatures. We demonstrate that in embryos that lack functional Mib2, muscle detachment is observed beginning in mid stage 15 and progresses rapidly, culminating in catastrophic degeneration and loss of most somatic muscles by stage 17. Notably, the degenerating muscles are positive for apoptosis markers, and inhibition of apoptosis in muscles prevents to a significant degree the muscle defects. Rescue experiments with Mib1 and Neuralized show further that these E3 ubiquitin ligases are not capable of ameliorating the muscle mutant phenotype of mib2. Our data suggest strongly that mib2 is involved in a novel Notch- and integrin-independent pathway that maintains the integrity of fully differentiated muscles and prevents their apoptotic degeneration.

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.…”

“…Previously it has been shown that apoptotic markers are upregulated in degenerating muscles (Nguyen et al, 2007). TUNEL stainings and anti-caspase 3 antibodies, apoptotic markers, labelled cells in both WT and mute 1281/Df embryos, below the plane of the myotubes.…”

FuRMAS: triggering myoblast fusion in Drosophila

“…This reprogramming requires the degradation of proteins specifically expressed in the fcm. Mind bomb 2 (Mib2) has been suggested to be involved in the degradation of the fcm identity factor Lame Duck (Carrasco-Rando and RuizGomez, 2008) and is further required for muscle integrity and stability (Nguyen et al, 2007).…”

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).…”