Rapid evolution of mammalian APLP1 as a synaptic adhesion molecule

Abstract Amyloid precursor protein (APP) family members are involved in essential neuronal development including neurite outgrowth, neuronal migration and maturation of synapse and neuromuscular junction. Among the APP gene family members, amyloid precursor-like protein 1 (APLP1) is selectively expr...

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Autores principales:	Wataru Onodera, Toru Asahi, Naoya Sawamura
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ce261874abb7437eb17029508357d765
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spelling	oai:doaj.org-article:ce261874abb7437eb17029508357d7652021-12-02T15:00:51ZRapid evolution of mammalian APLP1 as a synaptic adhesion molecule10.1038/s41598-021-90737-y2045-2322https://doaj.org/article/ce261874abb7437eb17029508357d7652021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-90737-yhttps://doaj.org/toc/2045-2322Abstract Amyloid precursor protein (APP) family members are involved in essential neuronal development including neurite outgrowth, neuronal migration and maturation of synapse and neuromuscular junction. Among the APP gene family members, amyloid precursor-like protein 1 (APLP1) is selectively expressed in neurons and has specialized functions during synaptogenesis. Although a potential role for APLP1 in neuronal evolution has been indicated, its precise evolutionary and functional contributions are unknown. This study shows the molecular evolution of the vertebrate APP family based on phylogenetic analysis, while contrasting the evolutionary differences within the APP family. Phylogenetic analysis showed 15 times higher substitution rate that is driven by positive selection at the stem branch of the mammalian APLP1, resulting in dissimilar protein sequences compared to APP/APLP2. Docking simulation identified one positively selected site in APLP1 that alters the heparin-binding site, which could affect its function, and dimerization rate. Furthermore, the evolutionary rate covariation between the mammalian APP family and synaptic adhesion molecules (SAMs) was confirmed, indicating that only APLP1 has evolved to gain synaptic adhesion property. Overall, our results suggest that the enhanced synaptogenesis property of APLP1 as one of the SAMs may have played a role in mammalian brain evolution.Wataru OnoderaToru AsahiNaoya SawamuraNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Wataru Onodera Toru Asahi Naoya Sawamura Rapid evolution of mammalian APLP1 as a synaptic adhesion molecule
description	Abstract Amyloid precursor protein (APP) family members are involved in essential neuronal development including neurite outgrowth, neuronal migration and maturation of synapse and neuromuscular junction. Among the APP gene family members, amyloid precursor-like protein 1 (APLP1) is selectively expressed in neurons and has specialized functions during synaptogenesis. Although a potential role for APLP1 in neuronal evolution has been indicated, its precise evolutionary and functional contributions are unknown. This study shows the molecular evolution of the vertebrate APP family based on phylogenetic analysis, while contrasting the evolutionary differences within the APP family. Phylogenetic analysis showed 15 times higher substitution rate that is driven by positive selection at the stem branch of the mammalian APLP1, resulting in dissimilar protein sequences compared to APP/APLP2. Docking simulation identified one positively selected site in APLP1 that alters the heparin-binding site, which could affect its function, and dimerization rate. Furthermore, the evolutionary rate covariation between the mammalian APP family and synaptic adhesion molecules (SAMs) was confirmed, indicating that only APLP1 has evolved to gain synaptic adhesion property. Overall, our results suggest that the enhanced synaptogenesis property of APLP1 as one of the SAMs may have played a role in mammalian brain evolution.
format	article
author	Wataru Onodera Toru Asahi Naoya Sawamura
author_facet	Wataru Onodera Toru Asahi Naoya Sawamura
author_sort	Wataru Onodera
title	Rapid evolution of mammalian APLP1 as a synaptic adhesion molecule
title_short	Rapid evolution of mammalian APLP1 as a synaptic adhesion molecule
title_full	Rapid evolution of mammalian APLP1 as a synaptic adhesion molecule
title_fullStr	Rapid evolution of mammalian APLP1 as a synaptic adhesion molecule
title_full_unstemmed	Rapid evolution of mammalian APLP1 as a synaptic adhesion molecule
title_sort	rapid evolution of mammalian aplp1 as a synaptic adhesion molecule
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/ce261874abb7437eb17029508357d765
work_keys_str_mv	AT wataruonodera rapidevolutionofmammalianaplp1asasynapticadhesionmolecule AT toruasahi rapidevolutionofmammalianaplp1asasynapticadhesionmolecule AT naoyasawamura rapidevolutionofmammalianaplp1asasynapticadhesionmolecule
_version_	1718389165072056320

Rapid evolution of mammalian APLP1 as a synaptic adhesion molecule

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