期刊
DEVELOPMENTAL CELL
卷 33, 期 6, 页码 644-659出版社
CELL PRESS
DOI: 10.1016/j.devcel.2015.04.014
关键词
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资金
- Light Microscopy Unit at the Institute of Biotechnology, University of Helsinki
- GBPM-Training Program
- FEBS Long-Term Fellowship
- Finnish Cultural Foundation
- Ministry of Education, Scientific Research and Techniques
- Astellas Foundation for Research on Metabolic Disorders and Scandinavia-Japan Sasakawa Foundation
- Academy of Finland [SA 1266351, SA 259799]
- University of Helsinki
- University of Aix-Marseille
- German Federal Ministry of Education and Research [01 EO 0901, 01GS0850, 01GS0851, 01GS0853, 01KX1012]
- Initiative and Networking Fund of the Helmholtz Association in the framework of the Helmholtz Alliance for Mental Research in an Ageing Society [HA-215]
- [ANR-13-BSU4-0012-01]
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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