Journal
FASEB JOURNAL
Volume 35, Issue 1, Pages -Publisher
WILEY
DOI: 10.1096/fj.202000351RR
Keywords
CTRP13; NPTXR; NPTX1; synapse; trans‐ synaptic
Categories
Funding
- NIDA NIH HHS [F32 DA031654] Funding Source: Medline
- NIH HHS [#UL1TR001108] Funding Source: Medline
Ask authors/readers for more resources
Synapses are the key structures through which neurons communicate, regulated by a variety of proteins. C1QL proteins, part of the C1q superfamily, act as synaptic organizers involved in crucial neuronal processes. The study shows that C1QL3 mediates a novel cell-cell adhesion complex involving ADGRB3 and two neuronal pentraxins, suggesting the formation of a new trans-synaptic adhesion complex.
Synapses are the fundamental structural unit by which neurons communicate. An orchestra of proteins regulates diverse synaptic functions, including synapse formation, maintenance, and elimination-synapse homeostasis. Some proteins of the larger C1q super-family are synaptic organizers involved in crucial neuronal processes in various brain regions. C1Q-like (C1QL) proteins bind to the adhesion G protein-coupled receptor B3 (ADGRB3) and act at synapses in a subset of circuits. To investigate the hypothesis that the secreted C1QL proteins mediate tripartite trans-synaptic adhesion complexes, we conducted an in vivo interactome study and identified new binding candidates. We demonstrate that C1QL3 mediates a novel cell-cell adhesion complex involving ADGRB3 and two neuronal pentraxins, NPTX1 and NPTXR. Analysis of single-cell RNA-Seq data from the cerebral cortex shows that C1ql3, Nptx1, and Nptxr are highly co-expressed in the same excitatory neurons. Thus, our results suggest the possibility that in vivo the three co-expressed proteins are presynaptically secreted and form a complex capable of binding to postsynaptically localized ADGRB3, thereby creating a novel trans-synaptic adhesion complex. Identifying new binding partners for C1QL proteins and deciphering their underlying molecular principles will accelerate our understanding of their role in synapse organization.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available