Premium
C1QL3 promotes cell‐cell adhesion by mediating complex formation between ADGRB3/BAI3 and neuronal pentraxins
Author(s) -
Sticco Matthew J.,
Peña Palomino Perla A.,
Lukacsovich David,
Thompson Brianna L.,
Földy Csaba,
Ressl Susanne,
Martinelli David C.
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.202000351rr
Subject(s) - cell adhesion , microbiology and biotechnology , cell , adhesion , chemistry , biology , biochemistry , organic chemistry
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.