Cargando…

Family of neural wiring receptors in bilaterians defined by phylogenetic, biochemical, and structural evidence

The evolution of complex nervous systems was accompanied by the expansion of numerous protein families, including cell-adhesion molecules, surface receptors, and their ligands. These proteins mediate axonal guidance, synapse targeting, and other neuronal wiring-related functions. Recently, 32 intera...

Descripción completa

Detalles Bibliográficos
Autores principales: Cheng, Shouqiang, Park, Yeonwoo, Kurleto, Justyna D., Jeon, Mili, Zinn, Kai, Thornton, Joseph W., Özkan, Engin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6525511/
https://www.ncbi.nlm.nih.gov/pubmed/31043568
http://dx.doi.org/10.1073/pnas.1818631116
_version_ 1783419740348219392
author Cheng, Shouqiang
Park, Yeonwoo
Kurleto, Justyna D.
Jeon, Mili
Zinn, Kai
Thornton, Joseph W.
Özkan, Engin
author_facet Cheng, Shouqiang
Park, Yeonwoo
Kurleto, Justyna D.
Jeon, Mili
Zinn, Kai
Thornton, Joseph W.
Özkan, Engin
author_sort Cheng, Shouqiang
collection PubMed
description The evolution of complex nervous systems was accompanied by the expansion of numerous protein families, including cell-adhesion molecules, surface receptors, and their ligands. These proteins mediate axonal guidance, synapse targeting, and other neuronal wiring-related functions. Recently, 32 interacting cell surface proteins belonging to two newly defined families of the Ig superfamily (IgSF) in fruit flies were discovered to label different subsets of neurons in the brain and ventral nerve cord. They have been shown to be involved in synaptic targeting and morphogenesis, retrograde signaling, and neuronal survival. Here, we show that these proteins, Dprs and DIPs, are members of a widely distributed family of two- and three-Ig domain molecules with neuronal wiring functions, which we refer to as Wirins. Beginning from a single ancestral Wirin gene in the last common ancestor of Bilateria, numerous gene duplications produced the heterophilic Dprs and DIPs in protostomes, along with two other subfamilies that diversified independently across protostome phyla. In deuterostomes, the ancestral Wirin evolved into the IgLON subfamily of neuronal receptors. We show that IgLONs interact with each other and that their complexes can be broken by mutations designed using homology models based on Dpr and DIP structures. The nematode orthologs ZIG-8 and RIG-5 also form heterophilic and homophilic complexes, and crystal structures reveal numerous apparently ancestral features shared with Dpr-DIP complexes. The evolutionary, biochemical, and structural relationships we demonstrate here provide insights into neural development and the rise of the metazoan nervous system.
format Online
Article
Text
id pubmed-6525511
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher National Academy of Sciences
record_format MEDLINE/PubMed
spelling pubmed-65255112019-05-28 Family of neural wiring receptors in bilaterians defined by phylogenetic, biochemical, and structural evidence Cheng, Shouqiang Park, Yeonwoo Kurleto, Justyna D. Jeon, Mili Zinn, Kai Thornton, Joseph W. Özkan, Engin Proc Natl Acad Sci U S A Biological Sciences The evolution of complex nervous systems was accompanied by the expansion of numerous protein families, including cell-adhesion molecules, surface receptors, and their ligands. These proteins mediate axonal guidance, synapse targeting, and other neuronal wiring-related functions. Recently, 32 interacting cell surface proteins belonging to two newly defined families of the Ig superfamily (IgSF) in fruit flies were discovered to label different subsets of neurons in the brain and ventral nerve cord. They have been shown to be involved in synaptic targeting and morphogenesis, retrograde signaling, and neuronal survival. Here, we show that these proteins, Dprs and DIPs, are members of a widely distributed family of two- and three-Ig domain molecules with neuronal wiring functions, which we refer to as Wirins. Beginning from a single ancestral Wirin gene in the last common ancestor of Bilateria, numerous gene duplications produced the heterophilic Dprs and DIPs in protostomes, along with two other subfamilies that diversified independently across protostome phyla. In deuterostomes, the ancestral Wirin evolved into the IgLON subfamily of neuronal receptors. We show that IgLONs interact with each other and that their complexes can be broken by mutations designed using homology models based on Dpr and DIP structures. The nematode orthologs ZIG-8 and RIG-5 also form heterophilic and homophilic complexes, and crystal structures reveal numerous apparently ancestral features shared with Dpr-DIP complexes. The evolutionary, biochemical, and structural relationships we demonstrate here provide insights into neural development and the rise of the metazoan nervous system. National Academy of Sciences 2019-05-14 2019-05-01 /pmc/articles/PMC6525511/ /pubmed/31043568 http://dx.doi.org/10.1073/pnas.1818631116 Text en Copyright © 2019 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/ https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Biological Sciences
Cheng, Shouqiang
Park, Yeonwoo
Kurleto, Justyna D.
Jeon, Mili
Zinn, Kai
Thornton, Joseph W.
Özkan, Engin
Family of neural wiring receptors in bilaterians defined by phylogenetic, biochemical, and structural evidence
title Family of neural wiring receptors in bilaterians defined by phylogenetic, biochemical, and structural evidence
title_full Family of neural wiring receptors in bilaterians defined by phylogenetic, biochemical, and structural evidence
title_fullStr Family of neural wiring receptors in bilaterians defined by phylogenetic, biochemical, and structural evidence
title_full_unstemmed Family of neural wiring receptors in bilaterians defined by phylogenetic, biochemical, and structural evidence
title_short Family of neural wiring receptors in bilaterians defined by phylogenetic, biochemical, and structural evidence
title_sort family of neural wiring receptors in bilaterians defined by phylogenetic, biochemical, and structural evidence
topic Biological Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6525511/
https://www.ncbi.nlm.nih.gov/pubmed/31043568
http://dx.doi.org/10.1073/pnas.1818631116
work_keys_str_mv AT chengshouqiang familyofneuralwiringreceptorsinbilateriansdefinedbyphylogeneticbiochemicalandstructuralevidence
AT parkyeonwoo familyofneuralwiringreceptorsinbilateriansdefinedbyphylogeneticbiochemicalandstructuralevidence
AT kurletojustynad familyofneuralwiringreceptorsinbilateriansdefinedbyphylogeneticbiochemicalandstructuralevidence
AT jeonmili familyofneuralwiringreceptorsinbilateriansdefinedbyphylogeneticbiochemicalandstructuralevidence
AT zinnkai familyofneuralwiringreceptorsinbilateriansdefinedbyphylogeneticbiochemicalandstructuralevidence
AT thorntonjosephw familyofneuralwiringreceptorsinbilateriansdefinedbyphylogeneticbiochemicalandstructuralevidence
AT ozkanengin familyofneuralwiringreceptorsinbilateriansdefinedbyphylogeneticbiochemicalandstructuralevidence