期刊
BIOCHEMICAL JOURNAL
卷 446, 期 -, 页码 321-330出版社
PORTLAND PRESS LTD
DOI: 10.1042/BJ20120808
关键词
autism; cross-linking; dimer; endoplasmic reticulum (ER) retention; oligomerization; synaptic adhesion; transmembrane domain
资金
- Max Planck Society
- German Research Foundation [GRK 521, FZT 103]
- European Commission (EUROSPIN)
- European Commission (SynSys)
- European Commission (EU-AIMS)
- Cure Autism Now Foundation
- Marie Curie IEF fellowship [274972]
Neuroligins are postsynaptic adhesion proteins involved in the establishment of functional synapses in the central nervous system. In rodents, four genes give rise to neuroligins that function at distinct synapses, with corresponding neurotransmitter and subtype specificities. In the present study, we examined the interactions between the different neuroligins by isolating endogenous oligomeric complexes using in situ cross-linking on primary neurons. Examining hippocampal, striatal, cerebellar and spinal cord cultures, we found that neuroligins form constitutive dimers, including homomers and, most notably, neuroligin 1/3 heteromers. Additionally, we found that neuroligin monomers are specifically retained in the secretory pathway through a cellular quality control mechanism that involves the neuroligin transmembrane domain, ensuring that dimerization occurs prior to cell surface trafficking. Lastly, we identified differences in the dimerization capacity of autism-associated neuroligin mutants, and found that neuroligin 3 R471C mutants can form heterodimers with neuroligin 1. The pervasive nature of neuroligin dimerization indicates that the unit of neuroligin function is the dimer, and raises intriguing possibilities of distinct heterodimer functions, and of interactions between native and mutant neuroligins contributing to disease phenotypes.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据