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 Ossowski; Tomi Taira; Pekka Lappalainen; Claudio Rivera; Pirta Hotulainen

doi:10.1016/j.devcel.2015.04.014

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

Research output: Contribution to journal › Article › peer-review

42 Citations (Scopus)

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 language	English
Pages (from-to)	644-659
Number of pages	16
Journal	Developmental Cell
Volume	33
Issue number	6
DOIs	https://doi.org/10.1016/j.devcel.2015.04.014
Publication status	Published - Jun 22 2015
Externally published	Yes

ASJC Scopus subject areas

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

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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

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

In: Developmental Cell, Vol. 33, No. 6, 22.06.2015, p. 644-659.

Research output: Contribution to journal › Article › peer-review

Saarikangas, J, Kourdougli, N, Senju, Y, Chazal, G, Segerstråle, M, Minkeviciene, R, Kuurne, J, Mattila, PK, Garrett, L, Hölter, SM, Becker, L, Racz, I, Hans, W, Klopstock, T, Wurst, W, Zimmer, A, Fuchs, H, Gailus-Durner, V, Hrabě de Angelis, M, von Ossowski, L, Taira, T, Lappalainen, P, Rivera, C & Hotulainen, P 2015, 'MIM-Induced Membrane Bending Promotes Dendritic Spine Initiation', Developmental Cell, vol. 33, no. 6, pp. 644-659. https://doi.org/10.1016/j.devcel.2015.04.014

Saarikangas, Juha ; Kourdougli, Nazim ; Senju, Yosuke ; Chazal, Genevieve ; Segerstråle, Mikael ; Minkeviciene, Rimante ; Kuurne, Jaakko ; Mattila, Pieta K. ; Garrett, Lillian ; Hölter, Sabine M. ; Becker, Lore ; Racz, Ildikó ; Hans, Wolfgang ; Klopstock, Thomas ; Wurst, Wolfgang ; Zimmer, Andreas ; Fuchs, Helmut ; Gailus-Durner, Valérie ; Hrabě de Angelis, Martin ; von Ossowski, Lotta ; Taira, Tomi ; Lappalainen, Pekka ; Rivera, Claudio ; Hotulainen, Pirta. / MIM-Induced Membrane Bending Promotes Dendritic Spine Initiation. In: Developmental Cell. 2015 ; Vol. 33, No. 6. pp. 644-659.

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title = "MIM-Induced Membrane Bending Promotes Dendritic Spine Initiation",

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.",

author = "Juha Saarikangas and Nazim Kourdougli and Yosuke Senju and Genevieve Chazal and Mikael Segerstr{\aa}le and Rimante Minkeviciene and Jaakko Kuurne and Mattila, {Pieta K.} and Lillian Garrett and H{\"o}lter, {Sabine M.} and Lore Becker and Ildik{\'o} Racz and Wolfgang Hans and Thomas Klopstock and Wolfgang Wurst and Andreas Zimmer and Helmut Fuchs and Val{\'e}rie Gailus-Durner and {Hrab{\v e} de Angelis}, Martin and {von Ossowski}, Lotta and Tomi Taira and Pekka Lappalainen and Claudio Rivera and Pirta Hotulainen",

note = "Funding Information: We thank Y. Barral, J. Einicke, M. F{\"a}rberb{\"o}ck, S. Kundt, S. L{\aa}gas, O. Nikkil{\"a}, 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-S{\"o}ldner 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). ",

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doi = "10.1016/j.devcel.2015.04.014",

language = "English",

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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).

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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MIM-Induced Membrane Bending Promotes Dendritic Spine Initiation

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