C1QL3 promotes cell-cell adhesion by mediating complex formation between ADGRB3/BAI3 and neuronal pentraxins.

Autor: Sticco MJ; Department of Neuroscience, University of Connecticut Health, Farmington, CT, USA., Peña Palomino PA; Department of Molecular and Cellular Biochemistry, Indiana University, Bloomington, IN, USA., Lukacsovich D; Laboratory of Neural Connectivity, Brain Research Institute, Faculties of Medicine and Science, University of Zürich, Zürich, Switzerland., Thompson BL; Department of Neuroscience, University of Connecticut Health, Farmington, CT, USA., Földy C; Laboratory of Neural Connectivity, Brain Research Institute, Faculties of Medicine and Science, University of Zürich, Zürich, Switzerland., Ressl S; Department of Molecular and Cellular Biochemistry, Indiana University, Bloomington, IN, USA.; Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA, USA.; Department of Neuroscience, The University of Texas at Austin, Austin, TX, USA., Martinelli DC; Department of Neuroscience, University of Connecticut Health, Farmington, CT, USA.; Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA, USA.; The Connecticut Institute for the Brain and Cognitive Sciences (IBACS), Storrs, CT, USA.
Jazyk: angličtina
Zdroj: FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2021 Jan; Vol. 35 (1), pp. e21194.
DOI: 10.1096/fj.202000351RR
Abstrakt: 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.
(© 2020 Federation of American Societies for Experimental Biology.)
Databáze: MEDLINE
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