Synapse type-specific proteomic dissection identifies IgSF8 as a hippocampal CA3 microcircuit organizer

被引：35

作者：

Apostolo, Nuno ^{[1
,2
]}

Smukowski, Samuel N. ^{[3
]}

Vanderlinden, Jeroen ^{[1
,2
]}

Condomitti, Giuseppe ^{[1
,2
]}

Rybakin, Vasily ^{[4
]}

ten Bos, Jolijn ^{[1
,2
]}

Trobiani, Laura ^{[5
]}

Portegies, Sybren ^{[1
,2
]}

Vennekens, Kristel M. ^{[1
,2
]}

Gounko, Natalia V. ^{[1
,2
,6
,7
]}

Comoletti, Davide ^{[5
,8
,9
,10
]}

Wierda, Keimpe D. ^{[1
,2
]}

Savas, Jeffrey N. ^{[3
]}

de Wit, Joris ^{[1
,2
]}

机构：

[1] VIB Ctr Brain & Dis Res, Herestr 49, B-3000 Leuven, Belgium

[2] Katholieke Univ Leuven, Dept Neurosci, Leuven Brain Inst, Herestr 49, B-3000 Leuven, Belgium

[3] Northwestern Univ, Feinberg Sch Med, Dept Neurol, Chicago, IL 60611 USA

[4] Katholieke Univ Leuven, Dept Microbiol & Immunol, REGA Inst, Immunobiol, Leuven, Belgium

[5] Victoria Univ Wellington, Sch Biol Sci, Wellington 6140, New Zealand

[6] Electro Microscopy Platform, Herestr 49, B-3000 Leuven, Belgium

[7] VIB BioImaging Core, Herestr 49, B-3000 Leuven, Belgium

[8] Rutgers State Univ, Child Hlth Inst New Jersey, New Brunswick, NJ 08901 USA

[9] Rutgers State Univ, Dept Neurosci, Robert Wood Johnson Med Sch, New Brunswick, NJ 08901 USA

[10] Rutgers State Univ, Dept Cell Biol, Robert Wood Johnson Med Sch, New Brunswick, NJ 08901 USA

来源：

NATURE COMMUNICATIONS | 2020年 / 11卷 / 01期

基金：

美国国家科学基金会; 欧洲研究理事会;

关键词：

CELL-ADHESION MOLECULE; KAINATE RECEPTOR SUBUNITS; LONG-TERM POTENTIATION; MOSSY FIBER BOUTONS; FEEDFORWARD INHIBITION; FAMILY PROTEINS; MICE DEFICIENT; DENTATE GYRUS; MOUSE; EWI-2;

D O I：

10.1038/s41467-020-18956-x

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Excitatory and inhibitory neurons are connected into microcircuits that generate circuit output. Central in the hippocampal CA3 microcircuit is the mossy fiber (MF) synapse, which provides powerful direct excitatory input and indirect feedforward inhibition to CA3 pyramidal neurons. Here, we dissect its cell-surface protein (CSP) composition to discover novel regulators of MF synaptic connectivity. Proteomic profiling of isolated MF synaptosomes uncovers a rich CSP composition, including many CSPs without synaptic function and several that are uncharacterized. Cell-surface interactome screening identifies IgSF8 as a neuronal receptor enriched in the MF pathway. Presynaptic Igsf8 deletion impairs MF synaptic architecture and robustly decreases the density of bouton filopodia that provide feedforward inhibition. Consequently, IgSF8 loss impairs excitation/inhibition balance and increases excitability of CA3 pyramidal neurons. Our results provide insight into the CSP landscape and interactome of a specific excitatory synapse and reveal IgSF8 as a critical regulator of CA3 microcircuit connectivity and function.

引用

页数：21

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