Molecular mechanisms underlying the evolution of the slp76 signalosome

Abstract The well-defined mammalian slp76-signalosome is crucial for T-cell immune response, yet whether slp76-signalosome exists in invertebrates and how it evolved remain unknown. Here we investigated slp76-signalosome from an evolutionary perspective in amphioxus Branchiostoma belcheri (bb). We p...

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Autores principales:	Xuemei Qu, Xin Lan, Chong Deng, Jiatao Zhou, Jingjing Du, Shengfeng Huang, Yingqiu Li
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5f328bd4ad194a609be5029ec4f2df2d
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spelling	oai:doaj.org-article:5f328bd4ad194a609be5029ec4f2df2d2021-12-02T12:32:43ZMolecular mechanisms underlying the evolution of the slp76 signalosome10.1038/s41598-017-01660-02045-2322https://doaj.org/article/5f328bd4ad194a609be5029ec4f2df2d2017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01660-0https://doaj.org/toc/2045-2322Abstract The well-defined mammalian slp76-signalosome is crucial for T-cell immune response, yet whether slp76-signalosome exists in invertebrates and how it evolved remain unknown. Here we investigated slp76-signalosome from an evolutionary perspective in amphioxus Branchiostoma belcheri (bb). We proved slp76-signalosome components bbslp76, bbGADS and bbItk are present in amphioxus and bbslp76 interacts with bbGADS and bbItk, but differences exist between the interaction manners within slp76-signalosome components of amphioxus and human (h). Specifically, bbslp76 has a unique WW-domain that blocked its association with hItk and decreased TCR-induced tyrosine-phosphorylation and NFAT-activation. Deletion of WW-domain shifted the constitutive association between bbslp76 and hPLCγ1 to a TCR-enhanced association. Among slp76-signalosome, the interaction between slp76 and PLCγ1 is the most conserved and the binding between Itk and slp76 evolved from constitutive to stimulation-regulated. Sequence alignment and 3D structural analysis of slp76-signalosome molecules from keystone species indicated slp76 evolved into a more unfolded and flexible adaptor due to lack of WW-domain and several low-complexity-regions (LCRs) while GADS turned into a larger protein by a LCR gain, thus preparing more space for nucleating the coevolving slp76-signalosome. Altogether, through deletion of WW-domain and manipulation of LCRs, slp76-signalosome evolves from a rigid and stimulation-insensitive to a more flexible and stimulation-responding complex.Xuemei QuXin LanChong DengJiatao ZhouJingjing DuShengfeng HuangYingqiu LiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Xuemei Qu Xin Lan Chong Deng Jiatao Zhou Jingjing Du Shengfeng Huang Yingqiu Li Molecular mechanisms underlying the evolution of the slp76 signalosome
description	Abstract The well-defined mammalian slp76-signalosome is crucial for T-cell immune response, yet whether slp76-signalosome exists in invertebrates and how it evolved remain unknown. Here we investigated slp76-signalosome from an evolutionary perspective in amphioxus Branchiostoma belcheri (bb). We proved slp76-signalosome components bbslp76, bbGADS and bbItk are present in amphioxus and bbslp76 interacts with bbGADS and bbItk, but differences exist between the interaction manners within slp76-signalosome components of amphioxus and human (h). Specifically, bbslp76 has a unique WW-domain that blocked its association with hItk and decreased TCR-induced tyrosine-phosphorylation and NFAT-activation. Deletion of WW-domain shifted the constitutive association between bbslp76 and hPLCγ1 to a TCR-enhanced association. Among slp76-signalosome, the interaction between slp76 and PLCγ1 is the most conserved and the binding between Itk and slp76 evolved from constitutive to stimulation-regulated. Sequence alignment and 3D structural analysis of slp76-signalosome molecules from keystone species indicated slp76 evolved into a more unfolded and flexible adaptor due to lack of WW-domain and several low-complexity-regions (LCRs) while GADS turned into a larger protein by a LCR gain, thus preparing more space for nucleating the coevolving slp76-signalosome. Altogether, through deletion of WW-domain and manipulation of LCRs, slp76-signalosome evolves from a rigid and stimulation-insensitive to a more flexible and stimulation-responding complex.
format	article
author	Xuemei Qu Xin Lan Chong Deng Jiatao Zhou Jingjing Du Shengfeng Huang Yingqiu Li
author_facet	Xuemei Qu Xin Lan Chong Deng Jiatao Zhou Jingjing Du Shengfeng Huang Yingqiu Li
author_sort	Xuemei Qu
title	Molecular mechanisms underlying the evolution of the slp76 signalosome
title_short	Molecular mechanisms underlying the evolution of the slp76 signalosome
title_full	Molecular mechanisms underlying the evolution of the slp76 signalosome
title_fullStr	Molecular mechanisms underlying the evolution of the slp76 signalosome
title_full_unstemmed	Molecular mechanisms underlying the evolution of the slp76 signalosome
title_sort	molecular mechanisms underlying the evolution of the slp76 signalosome
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/5f328bd4ad194a609be5029ec4f2df2d
work_keys_str_mv	AT xuemeiqu molecularmechanismsunderlyingtheevolutionoftheslp76signalosome AT xinlan molecularmechanismsunderlyingtheevolutionoftheslp76signalosome AT chongdeng molecularmechanismsunderlyingtheevolutionoftheslp76signalosome AT jiataozhou molecularmechanismsunderlyingtheevolutionoftheslp76signalosome AT jingjingdu molecularmechanismsunderlyingtheevolutionoftheslp76signalosome AT shengfenghuang molecularmechanismsunderlyingtheevolutionoftheslp76signalosome AT yingqiuli molecularmechanismsunderlyingtheevolutionoftheslp76signalosome
_version_	1718393980814622720

Molecular mechanisms underlying the evolution of the slp76 signalosome

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