Expression pattern of sorting nexin 25 in temporal lobe epilepsy: A study on patients and pilocarpine-induced rats

Du, Yingshi; Zou, Yan; Yu, Wei; Shi, Rui; Zhang, Man; Yang, Wenxiu; Duan, Jingxi; Deng, Yongtao; Wang, Xuefeng; Lü, Yang

doi:10.1016/j.brainres.2013.03.005

Cited by 18 publications

(18 citation statements)

References 18 publications

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“…Besides the PX domain, SNX25 contains a RGS domain just upstream of PX domain, and two uncharacterized domains: PXA and PXC, which are located at the Nand C terminus, respectively [8]. Some recent studies have demonstrated that SNX25 could negatively regulate transforming growth factor b (TGF-b) signaling by enhancing receptor degradation [9] and is involved in the development of temporal lobe epilepsy (TLE) as it is significantly overexpressed in TLE patients [10]. However, the exact function of SNX25 has not been well characterized till now, as well as the mechanism of how SNX25 localizes to endosomal membrane.…”

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confidence: 99%

Structure of the PX domain of SNX25 reveals a novel phospholipid recognition model by dimerization in the PX domain

Zhu

et al. 2017

FEBS Letters

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SNX25, a regulator of GPCR signaling-phox-homology (PX) domain containing sorting nexin (SNX) member, has been proposed to be involved in the lysosomal degradation of the transforming growth factor β receptor and the development of temporal lobe epilepsy. Targeting to the endosomal membranes by the specific binding of phosphorylated phosphatidylinositols (PIPs) through the PX domain is critical for the function of SNXs. However, the mechanism for SNX25-PX targeting to the endosomes remains unclear. Here, we demonstrate that the PX domain of zebrafish SNX25 (zSNX25-PX) is capable of binding to PI3P only in its dimeric form. We also present the crystal structure of zSNX25-PX. Combined with biochemical experiments, we further identify a potential PI3P-binding region and propose a novel PI-binding model based on dimerization in the PX domain of SNXs.

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confidence: 99%

Structure of the PX domain of SNX25 reveals a novel phospholipid recognition model by dimerization in the PX domain

Zhu

et al. 2017

FEBS Letters

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“…Recently Hao and colleagues (17) demonstrated a role for SNX25 as a regulator of transforming growth factor ␤ (TGF-␤) signaling, binding to and promoting the lysosomal trafficking and degradation of TGF-␤ receptors (T␤Rs). Its increased expression in the temporal cortex has also been correlated with temporal lobe epilepsy, although its direct role in the disease has not been confirmed (18). The SNX14 protein is expressed in motor neurons (19) and recent studies suggest that the Snx14 gene is paternally imprinted in neuronal cells, where it promotes synaptic transmission through unknown mechanisms (20).…”

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confidence: 99%

Structural Basis for Different Phosphoinositide Specificities of the PX Domains of Sorting Nexins Regulating G-protein Signaling

Mas

Norwood

Bugarčić

et al. 2014

Journal of Biological Chemistry

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“…The other significant connections of community C ( Fig 6B ) occur with community A—where are located SNX25 and ARPC5L , markers of intractable epilepsy—and with communities H and B which harbor, respectively, the genes MTA1 (a high-hub in E-DE community I, functionally described above) and RBPL1 , regulators of two epilepsy-associated genes ( HDAC2 and PAX6 , targets of the antiepileptic drug Valproate). The hub SNX25 codes for Sorting Nexin 25, a PX domain protein which modulates TGF-beta signaling pathway and is involved in epileptogenesis and TLE development [ 106 ]. SNX25 is a biomarker of intractable epilepsy, being overexpressed in TLE patients [ 106 ].…”

Section: Resultsmentioning

confidence: 99%

Community Structure Analysis of Transcriptional Networks Reveals Distinct Molecular Pathways for Early- and Late-Onset Temporal Lobe Epilepsy with Childhood Febrile Seizures

et al. 2015

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Age at epilepsy onset has a broad impact on brain plasticity and epilepsy pathomechanisms. Prolonged febrile seizures in early childhood (FS) constitute an initial precipitating insult (IPI) commonly associated with mesial temporal lobe epilepsy (MTLE). FS-MTLE patients may have early disease onset, i.e. just after the IPI, in early childhood, or late-onset, ranging from mid-adolescence to early adult life. The mechanisms governing early (E) or late (L) disease onset are largely unknown. In order to unveil the molecular pathways underlying E and L subtypes of FS-MTLE we investigated global gene expression in hippocampal CA3 explants of FS-MTLE patients submitted to hippocampectomy. Gene coexpression networks (GCNs) were obtained for the E and L patient groups. A network-based approach for GCN analysis was employed allowing: i) the visualization and analysis of differentially expressed (DE) and complete (CO) - all valid GO annotated transcripts - GCNs for the E and L groups; ii) the study of interactions between all the system’s constituents based on community detection and coarse-grained community structure methods. We found that the E-DE communities with strongest connection weights harbor highly connected genes mainly related to neural excitability and febrile seizures, whereas in L-DE communities these genes are not only involved in network excitability but also playing roles in other epilepsy-related processes. Inversely, in E-CO the strongly connected communities are related to compensatory pathways (seizure inhibition, neuronal survival and responses to stress conditions) while in L-CO these communities harbor several genes related to pro-epileptic effects, seizure-related mechanisms and vulnerability to epilepsy. These results fit the concept, based on fMRI and behavioral studies, that early onset epilepsies, although impacting more severely the hippocampus, are associated to compensatory mechanisms, while in late MTLE development the brain is less able to generate adaptive mechanisms, what has implications for epilepsy management and drug discovery.

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Expression pattern of sorting nexin 25 in temporal lobe epilepsy: A study on patients and pilocarpine-induced rats

Cited by 18 publications

References 18 publications

Structure of the PX domain of SNX25 reveals a novel phospholipid recognition model by dimerization in the PX domain

Structure of the PX domain of SNX25 reveals a novel phospholipid recognition model by dimerization in the PX domain

Structural Basis for Different Phosphoinositide Specificities of the PX Domains of Sorting Nexins Regulating G-protein Signaling

Community Structure Analysis of Transcriptional Networks Reveals Distinct Molecular Pathways for Early- and Late-Onset Temporal Lobe Epilepsy with Childhood Febrile Seizures

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