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 | |
| Publication status | Published - Jun 22 2015 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Molecular Biology
- Biochemistry, Genetics and Molecular Biology(all)
- Developmental Biology
- Cell Biology
Cite this
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
}
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 -