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 journalArticle

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

Fingerprint

Dendritic Spines
Actins
Spine
Membranes
Cell membranes
Phosphatidylinositols
Elongation
Chemical activation
Polymerization
Defects
Morphogenesis
Synaptic Transmission
Cell Membrane
Proteins

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., ... 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 journalArticle

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 J, Kourdougli N, Senju Y, Chazal G, Segerstråle M, Minkeviciene R et al. MIM-Induced Membrane Bending Promotes Dendritic Spine Initiation. Developmental Cell. 2015 Jun 22;33(6):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.
@article{e1ed74d261a54fda9ff8768d8509aff3,
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 {Hrabě de Angelis}, Martin and {von Ossowski}, Lotta and Tomi Taira and Pekka Lappalainen and Claudio Rivera and Pirta Hotulainen",
year = "2015",
month = "6",
day = "22",
doi = "10.1016/j.devcel.2015.04.014",
language = "English",
volume = "33",
pages = "644--659",
journal = "Developmental Cell",
issn = "1534-5807",
publisher = "Cell Press",
number = "6",

}

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

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.

UR - http://www.scopus.com/inward/record.url?scp=84937627872&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84937627872&partnerID=8YFLogxK

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 -