The actin polymerization factor Diaphanous and the actin severing protein Flightless I collaborate to regulate sarcomere size

Regulation of the Evolutionarily Conserved Muscle Myofibrillar Matrix by Cell Type Dependent and Independent Mechanisms

“…Actin ( Figure 4b,d ), myosin filaments ( Supplementary Video 10 ), and z-disk structures ( Supplementary Video 12 ) can each be observed in the thin myofibrillar segments suggesting that the major sarcomeric components are retained by these branches. While there have been few volume electron microscopy studies of Drosophila muscle 34 with which to compare our data, the light microscopic images of NCDN KD muscles ( Figure 4b,d ) are reminiscent of previous reports describing IF muscle sarcomere fraying 22, 50 . In fact, loss of diaphanous ( Dia ), an actin polymerization factor from the formin family, has been shown to induce fraying of Drosophila IF muscle myofibrils 22 .…”

“…These data combined with the similarities in cellular volume occupied by the contractile apparatus, mitochondria, and SRT between the Drosophila leg (Figure 1g) and mammalian slow-twitch oxidative muscles 1,25 and between the TDT (Figure 1g) and mammalian fast-twitch glycolytic muscles 6,16 suggest that Drosophila tubular muscles provide an ideal model system to investigate the mechanisms of myofibrillar connectivity. Conversely, the near perfect circular cylindrical shape and complete lack of sarcomere branching in the fibrillar IF muscle myofibrils (Figure 1a,e), in addition to the very low SRT content (Figure 1g) are unlike any known mammalian muscle, including the often compared cardiac muscle cell 22,24,34,40,41 in which myofibrillar networks are indeed formed 11 .…”

“…While there have been few volume electron microscopy studies of Drosophila muscle 34 with which to compare our data, the light microscopic images of NCDN KD muscles (Figure 4b,d) are reminiscent of previous reports describing IF muscle sarcomere fraying 22, 50 . In fact, loss of diaphanous (Dia), an actin polymerization factor from the formin family, has been shown to induce fraying of Drosophila IF muscle myofibrils 22 . Interestingly, mammalian orthologs of Dia (Dia1) and NCDN (NCDN) are known to be interacting partners where NCDN can inhibit Dia1-induced neurite outgrowth, albeit not through regulation of actin polymerization activity 38 .…”

“…Additionally, evidence of sarcomere branching can be seen in muscle images from fish 13 , chickens 14, 15 , and frogs 16 in addition to mice 12, 17 and humans 11, 18, 19 suggesting that myofibrillar networks may be conserved across vertebrate species. Conversely, insect fibrillar muscles, such as the commonly studied Drosophila indirect flight (IF) muscle, are known to be made up of the textbook individual myofibrils running the entire length of the muscle cell 20, 21, 22 , implying that a myofibrillar matrix may not occur in invertebrate muscles. However, the majority of Drosophila muscle cells are tubular, rather than fibrillar in nature 23 , and the connectivity of sarcomeres within tubular muscles remains unclear.…”

Crosstalk between myosin II and formin functions in the regulation of force generation and actomyosin dynamics in stress fibers

“…Formin molecules can multimerize [73,74] and can be part of molecular complexes (asters, nodes, vertices) connecting the plus ends of actin filaments together [75][76][77][78]. In particular, formins play an important role in the structural organization of muscle sarcomeres [79][80][81]. In addition, some formins demonstrate significant actin cross linking function [82,83], which in principle could be inhibited by SMIFH2.…”