TY - JOUR
T1 - MIM-Induced Membrane Bending Promotes Dendritic Spine Initiation
AU - Saarikangas, Juha
AU - Kourdougli, Nazim
AU - Senju, Yosuke
AU - Chazal, Genevieve
AU - Segerstråle, Mikael
AU - Minkeviciene, Rimante
AU - Kuurne, Jaakko
AU - Mattila, Pieta K.
AU - Garrett, Lillian
AU - Hölter, Sabine M.
AU - Becker, Lore
AU - Racz, Ildikó
AU - Hans, Wolfgang
AU - Klopstock, Thomas
AU - Wurst, Wolfgang
AU - Zimmer, Andreas
AU - Fuchs, Helmut
AU - Gailus-Durner, Valérie
AU - Hrabě de Angelis, Martin
AU - von Ossowski, Lotta
AU - Taira, Tomi
AU - Lappalainen, Pekka
AU - Rivera, Claudio
AU - Hotulainen, Pirta
N1 - Funding Information:
We thank Y. Barral, J. Einicke, M. Färberböck, S. Kundt, S. Lågas, O. Nikkilä, V. Paavilainen, Y. Sonntag, R. Seeliger B. Sperling, A. Wohlbier, and H. Zhao, as well as the GMC animal caretaker team and the Light Microscopy Unit at the Institute of Biotechnology, University of Helsinki for support and expert technical assistance. We are grateful to T. Balla, G. Garner, L. Machesky, J. Taunton, M. Vartiainen, and R. Wedlich-Söldner for kindly providing plasmid constructs. This work was supported by GBPM-Training Program, a FEBS Long-Term Fellowship and Finnish Cultural Foundation (to J.S.); the Ministry of Education, Scientific Research and Techniques (to N.K.); Astellas Foundation for Research on Metabolic Disorders and Scandinavia-Japan Sasakawa Foundation (to Y.S.); Academy of Finland (to P.H. [SA 1266351], P.L., and C.R. [SA 259799]); University of Helsinki, University of Aix-Marseille and ANR-13-BSU4-0012-01 (to C.R.); the German Federal Ministry of Education and Research grants to the German Center for Vertigo and Balance Disorders (grant 01 EO 0901), to the German Center for Neurodegenerative Diseases (DZNE), and to the GMC (NGFN-Plus grants 01GS0850, 01GS0851, 01GS0853; Infrafrontier grant 01KX1012); and the Initiative and Networking Fund of the Helmholtz Association in the framework of the Helmholtz Alliance for Mental Research in an Ageing Society (HA-215).
Publisher Copyright:
© 2015 Elsevier Inc.
PY - 2015/6/22
Y1 - 2015/6/22
N2 - 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.
AB - 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.
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U2 - 10.1016/j.devcel.2015.04.014
DO - 10.1016/j.devcel.2015.04.014
M3 - Article
C2 - 26051541
AN - SCOPUS:84937627872
VL - 33
SP - 644
EP - 659
JO - Developmental Cell
JF - Developmental Cell
SN - 1534-5807
IS - 6
ER -