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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 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 hPLC?1 to a TCR-enhanced association. Among slp76-signalosome, the interaction between slp76 and PLC?1 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.

SUBMITTER: Qu X

PROVIDER: S-EPMC5431462 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Molecular mechanisms underlying the evolution of the slp76 signalosome.

Qu Xuemei X Lan Xin X Deng Chong C Zhou Jiatao J Du Jingjing J Huang Shengfeng S Li Yingqiu Y

Scientific reports 20170504 1

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 ...[more]

PMID: 28473706

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Project description:Fever implies a significant increase in corporal temperature that aids toward the resolution of infective processes such as viral disease. The majority of vertebrate species are not homeothermic therefore must rely upon the environment for temperature regulation. Here we show that in the zebrafish an artificial viral infection, induced by poly (I:C), induces a fever response regulated by the behavioral choice of temperature. We recorded 12 h of the diurnal cycle in zebrafish previously treated (first 12 hours dark cycle) with the pyrogen, poly (I:C) [10 μg⋅kg-1]. Fish, n=10, were held in a thermal gradient (36-180C) separated into 7 interconnected chambers. Presence or absence of individuals in each chamber was recorded each 15 minutes throughout the 12 hour period. After the experimental period we dissected whole brains for microarray analysis. In monitored zebrafish intraperitoneal treatment with poly (I:C) induced a febrile behaviour with significantly elevated temperature preference (T of about 32ºC) in stark contrast with the observed frequency for saline-injected fish (28ºC). Microarray analyses uncovered significant shifts in transcriptional activity that were highly directed in the poly (I:C)-treated fish housed in the thermal gradient. When compared to gene expression profiles from poly (I:C)-treated fish deprived of a thermal gradient we observed a less intense specific to the poly (I:C) challenge and interestingly observed a scattered generalised stress response. Our results highlight the influence of temperature preference in the development of the immune response in zebrafish. Fever induced gene expression in zebrafish brain was measured at 24 after intra peritoneal injection with 1mg*Kg-1 of Poly (I:C) in zebrafish. Four independent experiments were performed to explore the transcriptomic profile induced by animals injected by Poly (I:C) with/whithout thermal gradient, saline solution (PBS), or control using different animals for each experiment.

Dataset Information

Molecular mechanisms underlying the evolution of the slp76 signalosome.

Publications

Molecular mechanisms underlying the evolution of the slp76 signalosome.

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