title: The Strip-Hippo Pathway Regulates Synaptic Terminal Formation by Modulating Actin Organization at the Drosophila Neuromuscular Synapses.
abstract: Synapse formation requires the precise coordination of axon elongation, cytoskeletal stability, and diverse modes of cell signaling. The underlying mechanisms of this interplay, however, remain unclear. Here, we demonstrate that Strip, a component of the striatin-interacting phosphatase and kinase (STRIPAK) complex that regulates these processes, is required to ensure the proper development of synaptic boutons at the Drosophila neuromuscular junction. In doing so, Strip negatively regulates the activity of the Hippo (Hpo) pathway, an evolutionarily conserved regulator of organ size whose role in synapse formation is currently unappreciated. Strip functions genetically with Enabled, an actin assembly/elongation factor and the presumptive downstream target of Hpo signaling, to modulate local actin organization at synaptic termini. This regulation occurs independently of the transcriptional co-activator Yorkie, the canonical downstream target of the Hpo pathway. Our study identifies a previously unanticipated role of the Strip-Hippo pathway in synaptic development, linking cell signaling to actin organization.
authors.affiliation: Department of Genetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan; Department of Tropical Medicine, Center for Medical Entomology, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi Minato-ku, Tokyo 105-8461, Japan.
authors.forename: Chisako
authors.initials: C
authors.lastname: Sakuma
authors.affiliation: Department of Genetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Saito
authors.affiliation: Department of Genetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Umehara
authors.affiliation: Department of Brain Development and Neural Regeneration, Tokyo Metropolitan Institute of Medical Science, Setagaya-ku, Tokyo 156-8506, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Kamimura
authors.affiliation: Department of Brain Development and Neural Regeneration, Tokyo Metropolitan Institute of Medical Science, Setagaya-ku, Tokyo 156-8506, Japan.
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Maeda
authors.affiliation: Department of Biology, Stanford University, Stanford, CA 94305, USA.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Mosca
authors.affiliation: Department of Genetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan; AMED-CREST, Japan Agency for Medical Research and Development, 20F Yomiuri Shimbun Building 1-7-1 Otemachi, Chiyoda-ku, Tokyo 100-0004, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Miura
authors.affiliation: Department of Genetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan; AMED-CREST, Japan Agency for Medical Research and Development, 20F Yomiuri Shimbun Building 1-7-1 Otemachi, Chiyoda-ku, Tokyo 100-0004, Japan; Department of Biological Science, Graduate School of Science, Hiroshima University, 1-3-1 Kagamiyama, Higashi-Hiroshima, Hiroshima 739-8526, Japan. Electronic address: tchihara@hiroshima-u.ac.jp.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Chihara
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism / Q000648:ultrastructure; D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D007814:Larva / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D055495:Neurogenesis / Q000235:genetics; D009469:Neuromuscular Junction / Q000254:growth & development / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D017729:Presynaptic Terminals / Q000378:metabolism* / Q000648:ultrastructure; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D000091102:YAP-Signaling Proteins; D000099317:Hippo Kinases
chemical_list: D000199:Actins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D015534:Trans-Activators; D000091102:YAP-Signaling Proteins; C092744:ENA-VASP proteins; C503814:Yki protein, Drosophila; C499474:hpo protein, Drosophila; D000099317:Hippo Kinases