SHISA9

Last update 08 May 2025

Basic Info

Synonyms

Protein shisa-9, shisa family member 9, SHISA9

Introduction

Regulator of short-term neuronal synaptic plasticity in the dentate gyrus. Associates with AMPA receptors (ionotropic glutamate receptors) in synaptic spines and promotes AMPA receptor desensitization at excitatory synapses (By similarity).

100 Clinical Results associated with SHISA9

100 Translational Medicine associated with SHISA9

0 Patents (Medical) associated with SHISA9

Literatures (Medical) associated with SHISA9

01 May 2023·Nature microbiology

Modulation of virus-induced neuroinflammation by the autophagy receptor SHISA9 in mice.

Article

Author: Wang, Liqiu ; Yang, Shuai ; Cai, Sihui ; Liu, Qingxiang ; Cui, Jun ; Zhang, Chenqiu ; Jin, Shouheng ; Xian, Huifang ; Zheng, Yanyan

Microglia and astrocytes are subgroups of brain glia cells that support and protect neurons within the central nervous system (CNS). At early stages of viral infection in the CNS, they are predominant responding cells and lead to recruitment of peripheral immune cells for viral clearance. Inhibitor of nuclear factor κB kinase subunit epsilon (IKKi) is critical for type I interferon signalling and inflammation, which modulate heterogenic immune responses during CNS infection. Balanced autophagy is vital to maintain brain integrity, yet regulation of autophagy and immune activity within brain glia cells is poorly understood. Here we identify SHISA9 as an autophagy cargo receptor that mediates the autophagy-dependent degradation of IKKi during herpes simplex virus type 1 infection. IKKi is recognized by SHISA9 through unanchored K48-linked poly-ubiquitin chains and bridged to autophagosome membrane components GABARAPL1. Single-cell RNA sequencing analysis shows that SHISA9 has temporal characteristics while modulating both antiviral and inflammatory responses in microglia and astrocytes at different stages during viral infection. We found that Shisa9^-/- mice are highly susceptible to herpes simplex virus encephalitis, have pathogenic astrocytes and display more severe neuroinflammation compared with wild-type mice. Taken together, our study unravels a critical role of selective autophagy by orchestrating immune heterogeneity of different CNS resident cells through the SHISA9-IKKi axis.

01 May 2023·Pesticide Biochemistry and Physiology

Shisa reduces the sensitivity of homomeric RDL channel to GABA in the two-spotted spider mite, Tetranychus urticae Koch

Article

Author: Zhao, Chunqing ; Jiang, Jie ; Wang, Ying ; Chen, Yiqu ; Jia, Zhongqiang ; Zhang, Kexin ; Zhan, Enling ; Wang, Qiuxia ; Tang, Tao

The γ-aminobutyric acid receptors (GABARs) mediate fast inhibitory transmission in central nervous system of insects and are important targets of insecticides. An auxiliary subunit, Shisa7, was identified in mammals as a single-passing transmembrane protein. However, the homology gene(s) of Shisa in invertebrates has not been reported to date. In the present study, a homolog Shisa gene was identified from the two-spotted spider mite, Tetranychus urticae Koch. Its open reading frame had 927 base pairs and encoded 308 amino acid residues, which has a typical Shisa domain at 13th-181st amino acid residues. According to the phylogenetic tree, the invertebrate Shisa was categorized apart with those of vertebrate, and TuShisa showed closest relationship with the Shisa9 of velvet mite, Dinothrombium tinctorium (L.). In the electrophysiological assay with two-electrode voltage clamp, the GABA-activated TuRDL channel was functionally formed in the Africa clawed frog Xenopus laevis (Daudin) oocytes (EC₅₀ = 53.34 μM). No GABA-activated current could be observed in TuShisa-expressed oocytes, whereas TuShisa could reduce the sensitivity of TuRDL/TuShisa (mass ratio of 1: 4) channel to GABA. The homology structural models of TuRDL and TuShisa were built by the SWISS-MODEL server, their interaction was predicted using Z-DOCK and three predicted hydrogen bonds and interface residues were analysed by PyMOL. Meanwhile, the key interface residues of TuShisa affected the stability of complex were calculated by Discovery Studio 2019. In conclusion, the TuShisa, as the first reported invertebrate Shisa, was explored and functionally examined as the GABARs auxiliary subunit. Our findings provide a basis for research of invertebrate Shisa.

12 Jul 2022·Journal of Immunology Research

Construction of a Novel Clinical Stage-Related Gene Signature for Predicting Outcome and Immune Response in Hepatocellular Carcinoma

Article

Author: Hong, Guo-qing ; Zeng, Long-fei ; Luo, Qing ; Yang, Liu ; Lai, Xing

Hepatocellular carcinoma (HCC) with high heterogeneity is one of the most frequent malignant tumors. However, there were no studies to create a clinical stage-related gene signature for HCC patients. Differentially expressed genes (DEGs) associated with clinical stage of HCC were analyzed based on TCGA datasets. Functional enrichment analysis was carried out by the use of stage-related DEGs. Then, the least absolute shrinkage and selection operator (LASSO) regression and univariate Cox regression were performed to reduce the overfit and the number of genes for further analysis. Next, survival and ROC assays were carried out to demonstrate the model using TCGA. Functional analysis and immune microenvironment analysis related to stage-related DEGs were performed. Reverse transcriptase polymerase chain reaction (RT-PCR) and Cell Counting Kit-8 (CCK-8) assays were applied to examine the expression and function of PNCK in HCC. In this research, there were 21 DEGs between HCC specimens with stage (I-II) and HCC specimens with stage (III-IV), including 20 increased genes and 1 decreased genes. A novel seven-gene signature (including PITX2, PNCK, GLIS1, SCNN1G, MMP1, ZNF488, and SHISA9) was created for the prediction of outcomes of HCC patients. The ROC curves confirmed the prognostic value of the new model. Cox assays demonstrated that the seven-gene signature can independently forecast overall survival. The immune analysis revealed that patients with low risk score exhibited more immune activities. Moreover, we confirmed that PNCK expressions were distinctly increased in HCC, and its silence suppressed the proliferation of HCC cells. Overall, our research offered a robust and reliable gene signature which displayed an important value in the prediction of overall survival of HCC patients and might deliver more effective personalized therapies.

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