The Strip-Hippo Pathway Regulates Synaptic Terminal Formation by Modulating Actin Organization at the Drosophila Neuromuscular Synapses

Chisako Sakuma; Yoshie Saito; Tomoki Umehara; Keisuke Kamimura; Nobuaki Maeda; Timothy J Mosca; Masayuki Miura; Takahiro Chihara

doi:10.1016/j.celrep.2016.07.066

The Strip-Hippo Pathway Regulates Synaptic Terminal Formation by Modulating Actin Organization at the Drosophila Neuromuscular Synapses

Cell Rep. 2016 Aug 30;16(9):2289-97. doi: 10.1016/j.celrep.2016.07.066. Epub 2016 Aug 18.

Authors

Chisako Sakuma¹, Yoshie Saito², Tomoki Umehara², Keisuke Kamimura³, Nobuaki Maeda³, Timothy J Mosca⁴, Masayuki Miura⁵, Takahiro Chihara⁶

Affiliations

¹ 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.
² Department of Genetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
³ Department of Brain Development and Neural Regeneration, Tokyo Metropolitan Institute of Medical Science, Setagaya-ku, Tokyo 156-8506, Japan.
⁴ Department of Biology, Stanford University, Stanford, CA 94305, USA.
⁵ 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.
⁶ 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.

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.

MeSH terms

Actin Cytoskeleton / metabolism
Actin Cytoskeleton / ultrastructure
Actins / genetics
Actins / metabolism
Animals
DNA-Binding Proteins / genetics
DNA-Binding Proteins / metabolism
Drosophila Proteins / genetics*
Drosophila Proteins / metabolism
Drosophila melanogaster / genetics*
Drosophila melanogaster / growth & development
Drosophila melanogaster / metabolism
Gene Expression Regulation, Developmental
Intracellular Signaling Peptides and Proteins / genetics*
Intracellular Signaling Peptides and Proteins / metabolism
Larva / genetics
Larva / growth & development
Larva / metabolism
Nerve Tissue Proteins / genetics*
Nerve Tissue Proteins / metabolism
Neurogenesis / genetics
Neuromuscular Junction / growth & development
Neuromuscular Junction / metabolism*
Nuclear Proteins / genetics
Nuclear Proteins / metabolism
Presynaptic Terminals / metabolism*
Presynaptic Terminals / ultrastructure
Protein Serine-Threonine Kinases / genetics*
Protein Serine-Threonine Kinases / metabolism
Signal Transduction*
Trans-Activators / genetics
Trans-Activators / metabolism
YAP-Signaling Proteins

Substances

Actins
DNA-Binding Proteins
Drosophila Proteins
ENA-VASP proteins
Intracellular Signaling Peptides and Proteins
Nerve Tissue Proteins
Nuclear Proteins
Trans-Activators
YAP-Signaling Proteins
Yki protein, Drosophila
Protein Serine-Threonine Kinases
hpo protein, Drosophila

Abstract

MeSH terms

Substances

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