Structural basis for synaptic adhesion mediated by neuroligin-neurexin interactions

被引：80

作者：

Chen, Xiaoyan ^{[1
]}

Liu, Heli ^{[1
]}

Shim, Ann H. R. ^{[1
]}

Focia, Pamela J. ^{[1
]}

He, Xiaolin ^{[1
]}

机构：

[1] Northwestern Univ, Feinberg Sch Med, Dept Mol Pharmacol & Biol Chem, Chicago, IL 60611 USA

来源：

NATURE STRUCTURAL & MOLECULAR BIOLOGY | 2008年 / 15卷 / 01期

关键词：

D O I：

10.1038/nsmb1350

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The heterophilic synaptic adhesion molecules neuroligins and neurexins are essential for establishing and maintaining neuronal circuits by modulating the formation and maturation of synapses. The neuroligin-neurexin adhesion is Ca2+-dependent and regulated by alternative splicing. We report a structure of the complex at a resolution of 2.4 angstrom between the mouse neuroligin-1 (NL1) cholinesterase-like domain and the mouse neurexin-1 beta (NX1 beta) LNS (laminin, neurexin and sex hormone-binding globulin-like) domain. The structure revealed a delicate neuroligin-neurexin assembly mediated by a hydrophilic, Ca2+-mediated and solvent-supplemented interface, rendering it capable of being modulated by alternative splicing and other regulatory factors. Thermodynamic data supported a mechanism wherein splicing site B of NL1 acts by modulating a salt bridge at the edge of the NL1-NX1 beta interface. Mapping neuroligin mutations implicated in autism indicated that most such mutations are structurally destabilizing, supporting deficient neuroligin biosynthesis and processing as a common cause for this brain disorder.

引用

页码：50 / 56

页数：7

共 40 条

[1] A splice code for trans-synaptic cell adhesion mediated by binding of neuroligin 1 to α- and β-neurexins [J].

Boucard, AA ;

Chubykin, AA ;

Comoletti, D ;

Taylor, P ;

Südhof, TC .

NEURON, 2005, 48 (02) :229-236

[2] ACETYLCHOLINESTERASE INHIBITION BY FASCICULIN - CRYSTAL-STRUCTURE OF THE COMPLEX [J].

BOURNE, Y ;

TAYLOR, P ;

MARCHOT, P .

CELL, 1995, 83 (03) :503-512

[3] Crystallography & NMR system:: A new software suite for macromolecular structure determination [J].

Brunger, AT ;

Adams, PD ;

Clore, GM ;

DeLano, WL ;

Gros, P ;

Grosse-Kunstleve, RW ;

Jiang, JS ;

Kuszewski, J ;

Nilges, M ;

Pannu, NS ;

Read, RJ ;

Rice, LM ;

Simonson, T ;

Warren, GL .

ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, 1998, 54 :905-921

[4] Control of excitatory and inhibitory synapse formation by neuroligins [J].

Chih, B ;

Engelman, H ;

Scheiffele, P .

SCIENCE, 2005, 307 (5713) :1324-1328

[5] Disorder-associated mutations lead to functional inactivation of neuroligins [J].

Chih, B ;

Afridi, SK ;

Clark, L ;

Scheiffele, P .

HUMAN MOLECULAR GENETICS, 2004, 13 (14) :1471-1477

[6] Alternative splicing controls selective trans-synaptic interactions of the neuroligin-neurexin complex [J].

Chih, Ben ;

Gollan, Leora ;

Scheiffele, Peter .

NEURON, 2006, 51 (02) :171-178

[7] Dissection of synapse induction by neuroligins -: Effect of a neuroligin mutation associated with autism [J].

Chubykin, AA ;

Liu, XR ;

Comoletti, D ;

Tsigelny, I ;

Taylor, P ;

Südhof, TC .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (23) :22365-22374

[8] Activity-dependent validation of excitatory versus inhibitory synapses by neuroligin-1 versus neuroligin-2 [J].

Chubykin, Alexander A. ;

Atasoy, Deniz ;

Etherton, Mark R. ;

Brose, Nils ;

Kavalali, Ege T. ;

Gibson, Jay R. ;

Suedhof, Thomas C. .

NEURON, 2007, 54 (06) :919-931

[9] Characterization of the interaction of a recombinant soluble neuroligin-1 with neurexin-1β [J].

Comoletti, D ;

Flynn, R ;

Jennings, LL ;

Chubykin, A ;

Matsumura, T ;

Hasegawa, H ;

Südhof, TC ;

Taylor, P .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (50) :50497-50505

[10] The Arg451Cys-neuroligin-3 mutation associated with autism reveals a defect in protein processing [J].

Comoletti, D ;

De Jaco, A ;

Jennings, LL ;

Flynn, RE ;

Gaietta, G ;

Tsigelny, I ;

Ellisman, MH ;

Taylor, P .

JOURNAL OF NEUROSCIENCE, 2004, 24 (20) :4889-4893

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