MIM-Induced Membrane Bending Promotes Dendritic Spine Initiation

Juha Saarikangas, Nazim Kourdougli, Yosuke Senju, Genevieve Chazal, Mikael Segerstråle, Rimante Minkeviciene, Jaakko Kuurne, Pieta K. Mattila, Lillian Garrett, Sabine M. Hölter, Lore Becker, Ildikó Racz, Wolfgang Hans, Thomas Klopstock, Wolfgang Wurst, Andreas Zimmer, Helmut Fuchs, Valérie Gailus-Durner, Martin Hrabě de Angelis, Lotta von OssowskiTomi Taira, Pekka Lappalainen, Claudio Rivera, Pirta Hotulainen

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Abstract

Proper morphogenesis of neuronal dendritic spines is essential for the formation of functional synaptic networks. However, it is not known how spines are initiated. Here, we identify the inverse-BAR (I-BAR) protein MIM/MTSS1 as a nucleator of dendritic spines. MIM accumulated to future spine initiation sites in a PIP2-dependent manner and deformed the plasma membrane outward into a proto-protrusion via its I-BAR domain. Unexpectedly, the initial protrusion formation did not involve actin polymerization. However, PIP2-dependent activation of Arp2/3-mediated actin assembly was required for protrusion elongation. Overexpression of MIM increased the density of dendritic protrusions and suppressed spine maturation. In contrast, MIM deficiency led to decreased density of dendritic protrusions and larger spine heads. Moreover, MIM-deficient mice displayed altered glutamatergic synaptic transmission and compatible behavioral defects. Collectively, our data identify an important morphogenetic pathway, which initiates spine protrusions by coupling phosphoinositide signaling, direct membrane bending, and actin assembly to ensure proper synaptogenesis.

Original languageEnglish
Pages (from-to)644-659
Number of pages16
JournalDevelopmental Cell
Volume33
Issue number6
DOIs
Publication statusPublished - Jun 22 2015

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ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

Cite this

Saarikangas, J., Kourdougli, N., Senju, Y., Chazal, G., Segerstråle, M., Minkeviciene, R., Kuurne, J., Mattila, P. K., Garrett, L., Hölter, S. M., Becker, L., Racz, I., Hans, W., Klopstock, T., Wurst, W., Zimmer, A., Fuchs, H., Gailus-Durner, V., Hrabě de Angelis, M., ... Hotulainen, P. (2015). MIM-Induced Membrane Bending Promotes Dendritic Spine Initiation. Developmental Cell, 33(6), 644-659. https://doi.org/10.1016/j.devcel.2015.04.014