BMC Molecular & Cell Biology publishes Abi Karunendiran's paper on Drosophila larval muscle

Abiramy Karunendiran (PhD Student, Bryan Stewart Lab) had her paper Disruption of Drosophila larval muscle structure and function by UNC45 knockdown published by BMC Molecular and Cell Biology.

https://doi.org/10.1186/s12860-021-00373-7

Proper muscle function is heavily dependent on highly ordered protein complexes. UNC45 is a USC (named since this region is shared by three proteins UNC45/CRO1/She4P) chaperone that is necessary for myosin incorporation into the thick filaments. UNC45 is expressed throughout the entire Drosophila life cycle and it has been shown to be important during late embryogenesis when initial muscle development occurs. However, the effects of UNC45 manipulation at later developmental times, after muscle development, have not yet been studied. In this study, UNC45 was knocked down with RNAi in a manner that permitted survival to the pupal stage, allowing for characterization of sarcomere organization in the well-studied third instar larvae. Second harmonic generation (SHG), confocal and electron microscopy were utilized the study changes in the striated pattern of body wall muscles. We show diminished UNC45 signal and disorganization of myosin and z-disk proteins, leading to disorganization of the striated pattern. Concomitant alterations in both synaptic physiology and locomotor function were also found. Both nerve-stimulated response and spontaneous vesicle release were negatively affected, while larval movement was impaired. This study highlights the dependency of normal sarcomere structure on UNC45 expression. We confirm the known role of UNC45 for myosin localization and further show the I-Z-I complex is also disrupted. This suggests a broad need for UNC45 to maintain sarcomere integrity. Newly discovered changes in synaptic physiology reveal the likely presence of a homeostatic response to partially maintain synaptic strength and muscle function.