RESEARCH HIGHLIGHTS Nature Reviews Molecular Cell Biology | AOP, published online 12 January 2011; doi:10.1038/nrm3045 CYTOSKELETON allows nebulin to associate with N-WASP and recruit it to Z disks. So how does N-WASP induce actin N-WASP ‘muscles in’ on actin nucleation filament formation in myofibrils? As the actin nucleator actin-related protein 2/3 Muscle maturation and hypertrophy specifically in Z disks (where actin (ARP2/3) was not associated with require the activation of protein filaments anchor) in response to IGF1. myofibrils, another mechanism must synthesis and myofibrillogenesis. IGF1-mediated It colocalized here with α-actinin, which operate. Indeed, the authors showed Takano et al. now show that insulin-like anchors actin filaments. This correlated that N-WASP and nebulin cooperate growth factor 1 (IGF1) can mediate recruitment with actin filament formation, to polymerize actin through the two myofibrillogenesis through a pathway of N-WASP to indicating that the IGF1-mediated WASP homology 2 domains of N-WASP involving neural Wiskott–Aldrich Z disks might recruitment of N-WASP to Z disks might and the actin monomer-binding motifs syndrome protein (N-WASP) and the induce actin polymerization. of nebulin. sarcomeric protein nebulin. induce actin Next, the authors examined how Therefore, it seems that in myofibrils, Muscle cells are made up of polymerization. N-WASP is recruited to Z disks. They N-WASP and nebulin induce actin arrays of myofibrils (made during found that, following IGF1 treatment, polymerization independently of myofibrillogenesis), which consist of nebulin (which spans almost the entire ARP2/3. The resultant formation actin and myosin filaments. However, length of actin filaments) binds to the of actin filaments, together with it was unclear which proteins induce N-WASP Pro-rich region through its myosin filament assembly, induces actin polymerization in these SRC homology 3 domain to recruit it myofibrillogenesis. structures. Because N-WASP to Z disks. This interaction is mediated Rachel David induces actin polymerization in by the IGF1-induced activation of non-muscle cells, the authors phosphoinositide 3-kinase, which ORIGINAL RESEARCH PAPER Takano, K. et al. examined whether it might activates the kinase AKT to Nebulin and N-WASP cooperate to cause also do so in myofibrils. phosphorylate, and thus IGF-1-induced sarcomeric actin filament formation. Science 330, 1536–1540 (2010) They observed inhibit, glycogen synthase FURTHER READING Sparrow, J. C. & Schöck, F. that, during muscle kinase 3β (GSK3β). The initial steps of myofibril assembly: integrins regeneration, This prevents the GSK3 -mediated pave the way. Nature Rev. Mol. Cell Biol. 10, β 293–298 (2009) N-WASP localized phosphorylation of nebulin, which PHOTOALTO NATURE REVIEWS | MOLECULAR CELL BIOLOGY VOLUME 12 | FEBRUARY 2011 © 2011 Macmillan Publishers Limited. All rights reserved.