Overexpression of Drosophila NUAK or Constitutively-Active Formin-Like Promotes the Formation of Aberrant Myofibrils.

Abstract

Muscle development and maintenance is central to the normal functioning of animals. Muscle tissues exhibit high levels of activity and require the dynamic turnover of proteins. An actomyosin scaffold functions with additional proteins comprising the basic contractile subunit of striated muscle, known as the sarcomere. Drosophila muscles are similar to vertebrate muscles in composition and they share a similar mechanism of development. Drosophila NUAK (NUAK) is the homolog of NUAK1 and NUAK2 in vertebrates. NUAK belongs to the family of AMP-activated protein kinases (AMPKs), a group of proteins with broad and overlapping cellular targets. Here we confirm that NUAK dynamically modulates larval muscle sarcomere size as upregulation of NUAK produces longer sarcomeres, including increased thin filament lengths. Furthermore, NUAK overexpression results in aberrant myofibers above the nuclei plane, upregulation of Formin-like (Frl), and an increase in newly synthesized proteins at sites consistent with actin filament assembly. Expression of constitutively-active Frl also produces aberrant myofibers similar to NUAK overexpression. These results taken together strongly suggest a functional link between NUAK and Frl in myofibril formation in an in vivo setting.