{"database":"Pride","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Txt":["ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD063306/checksum.txt"],"Raw":["ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD063306/XNJ_CTF_3.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD063306/XNJ_CTF_2.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD063306/XNJ_CTF_1.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD063306/XNJ_N_GFP.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD063306/XNJ_GFP_3.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD063306/XNJ_N_CTF.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD063306/XNJ_GFP_2.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD063306/XNJ_GFP_1.raw"],"Other":["ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD063306/Analysis.zip"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"labhead_mail":["sunsuya@shsmu.edu.cn"],"submitter":["wubo Han"],"technology_type":["Mass Spectrometry","Gel-based experiment"],"disease":["Disease Free"],"software":["Not available"],"submitter_keywords":["Mouse","C-terminal fragment","Pirb","Hippocampus","Golgi apparatus"],"full_dataset_link":["https://www.ebi.ac.uk/pride/archive/projects/PXD063306"],"tissue":["Brain","Cns Neuron (sensu Nematoda And Protostomia)"],"sample_protocol":["PirB-CTF-HA was overecpressed in HEK293T cells. 48h after tranfection, cells were collected, homogenized at 4°C for 1h in lysis buffer, and immunoprecipitated with anti-HA beads for 4h at 4°C. After washing with lysis buffer, the beads were mixed with hippocampal homogenates from 8-week-old WT mice and incubated overnight at 4°C.Following multiple washes with lysis buffer, the immunoprecipitates were eluted from the beads and subjected to SDS-PAGE. The gel was cut for in-gel digestion, and the resulting tryptic peptides were analyzed by LC–MS/MS."],"repository":["Pride"],"quantification_method":[""],"modification":[""],"data_protocol":["The raw data of LC-MS/MS was analyzed using PEAKS Studio software. The peptide spectual counts were exported. The rank order of binding partners was determined based on the fold change in peptide counts of the detected proteins. And the protein locating at Golgi apparatus were regared as putatively binding partners."],"omics_type":["Proteomics"],"labhead":["Suya Sun"],"instrument_platform":[""],"labhead_affiliation":["Department of Neurology and Institute of Neurology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China."],"submission_type":["PARTIAL"],"species":["Mus Musculus (mouse)"],"submitter_mail":["349417183@qq.com"],"publication":["42231420 Han WB, Liu XD, Tang CF, Zheng J, Xu TL, Xu NJ, Sun S. Persistent PirB cleavage drives Golgi-directed trafficking deficits underlying neurodegeneration. Transl Neurodegener. 2026 15(1):26 10.1186/s40035-026-00553-5"],"submitter_affiliation":["Department of Neurology and Institute of Neurology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China."],"submitter_country":["China"],"pubmed_abstract":["<h4>Background</h4>Extensive research evidence indicates that neuronal immune receptors play a critical role in Alzheimer's disease (AD). However, it remains unclear how these receptors convert extracellular signals into cellular pathological changes. Proteolytic cleavage of membrane receptors serves as an unconventional pathway for reprogramming cellular functions, and the cleaved fragments often play important roles within the cell. Whether immune receptors mediate their effects in AD through this cleavage-dependent signaling mechanism remains to be clarified.<h4>Methods</h4>We performed proteomic screening of human cerebrospinal fluid to identify cleaved membrane proteins. Cleavage events were validated in postmortem AD brains, primary neurons, and APP/PS1 mice by immunoprecipitation, liquid chromatography-tandem mass spectrometry (LC-MS/MS), and immunofluorescence. Functional impacts were assessed through cathepsin D maturation assays, Retention Using Selective Hooks (RUSH) systems, live imaging of axonal transport, and behavioral tests (e.g., Barnes maze and fear conditioning). Therapeutic potential was evaluated by inhibiting the paired immunoglobulin-like receptor B (PirB) cleavage and overexpression of the GAT domain of Golgi-associated, gamma adaptin ear-containing, ARF binding protein 3 (GGA3).<h4>Results</h4>This study identified a pathogenic proteolytic pathway in AD patients and mouse models, which cleaves PirB, a mouse ortholog of human leukocyte immunoglobulin-like receptor B2 (LILRB2), upon Aβ exposure, generating a C-terminal fragment (PirB-CTF) that accumulated in the Golgi apparatus via retrograde transport. PirB-CTF bound to the GAT domain of GGA3, disrupting Golgi transport, impairing lysosomal maturation, and compromising anterograde synaptic vesicle transport. Inhibiting PirB cleavage or overexpressing GGA3-GAT restored Golgi function, reduced Aβ plaque burden and tau phosphorylation, and rescued memory deficits.<h4>Conclusion</h4>Our study revealed a non-canonical pathway in which proteolytic cleavage repurposes PirB into an intracellular disruptor of Golgi trafficking, directly coupling immune receptor activation to organelle dysfunction in AD. The PirB-CTF/GGA3 interface represents a promising therapeutic target for mitigating trafficking deficits and cognitive decline in neurodegenerative disorders."],"pubmed_title":["Persistent PirB cleavage drives Golgi-directed trafficking deficits underlying neurodegeneration."],"pubmed_authors":["Han Wu-Bo WB, Liu Xian-Dong XD, Tang Chang-Fei CF, Zheng Junke J, Xu Tian-Le TL, Xu Nan-Jie NJ, Sun Suya S"],"additional_accession":[]},"is_claimable":false,"name":"PirB-CTF LC-MS/MS in hippocampus","description":"Our result indicated PirB could undergo proteolytic process, generating a C-terminal fragment (PirB-CTF). We found PirB-CTF can translocates to the Golgi apparatus, disrupting Golgi-dependent protein transport. To investigate the novel binding partners which mediated the effect of PirB-CTF, we used mass spectrometry analysis.","dates":{"publication":"2026-06-08","submission":"2025-04-25"},"accession":"PXD063306","cross_references":{"TAXONOMY":["NEWT:6945","NEWT:3555","NEWT:2","NEWT:157546","NEWT:35554","NEWT:38942","NEWT:307972","NEWT:32046","NEWT:544496","NEWT:2042546","NEWT:45351","NEWT:43179","NEWT:4513","NEWT:5722","NEWT:55153","NCBITaxon:10407","NEWT:1736309","NEWT:1211601","NEWT:876138","NEWT:237561","NEWT:5833","NEWT:6928","NEWT:10036","NEWT:36745","NEWT:1351","NEWT:1438992","NEWT:2649997","NEWT:272563","NEWT:224326","NCBITaxon:79857","NEWT:1096976","NEWT:95648","NEWT:3885","NEWT:3888","NEWT:1589","NEWT:135622","NEWT:6915","NEWT:3649","NEWT:101510","NEWT:3880","NEWT:272559","NEWT:3641","NEWT:383379","NEWT:10029","NEWT:1000589","NEWT:85962","NEWT:317447","NEWT:7955","NEWT:7959","NEWT:2261","NEWT:31156","NEWT:4565","NEWT:1264690","NEWT:515619","NEWT:192875","NEWT:34305","NEWT:59729","NCBITaxon:183674","NEWT:224308","NEWT:84645","NEWT:626528","NEWT:139927","NEWT:4558","NEWT:209285","NEWT:1283","NEWT:931281","NEWT:4550","NEWT:1000561","NEWT:197","NCBITaxon:79824","NEWT:4787","NCBITaxon:4563","NEWT:5755","NEWT:44689","NEWT:3218","NEWT:5759","NEWT:1736231","NEWT:1270","NEWT:2242","NEWT:4784","NEWT:11320","NEWT:360106","NEWT:287","NEWT:10117","NEWT:10239","NEWT:10116","NEWT:1280","NEWT:1735272","NEWT:83334","NEWT:83332","NEWT:44685","NEWT:317513","NEWT:1148","NEWT:580240","NEWT:294128","NEWT:11676","NEWT:55571","NEWT:100226","NEWT:4530","NEWT:4896","NEWT:75058","NEWT:13616","NEWT:1094343","NEWT:296543","NEWT:1773","NEWT:1895","NEWT:1182590","NEWT:935293","NEWT:64152","NEWT:4924","NEWT:749200","NEWT:990346","NEWT:145953","NEWT:257309","NEWT:100816","NEWT:263","NEWT:230741","NEWT:52283","NEWT:284812","NCBITaxon:1313","NEWT:43330","NEWT:408169","NEWT:44544","NEWT:4911","NEWT:645463","NEWT:3702","NEWT:129249","NEWT:990119","NEWT:408172","NEWT:408170","NEWT:493760","NEWT:260710","NEWT:257313","NEWT:400772","NEWT:3708","NEWT:128161","NEWT:332648","NEWT:106592","NEWT:536231","NEWT:1432138","NEWT:10312","NEWT:1424507","NCBITaxon:1773","NEWT:9598","NEWT:8030","NEWT:1639","NEWT:188229","NEWT:3818","NEWT:480","NEWT:4909","NEWT:67767","NEWT:432359","NEWT:46835","NEWT:2711","NEWT:376686","NEWT:95486","NEWT:9103","NEWT:29159","NEWT:10306","NCBITaxon:2759","NEWT:1233435","NEWT:8022","NEWT:145943","NCBITaxon:4932","NEWT:595536","NEWT:240906","NEWT:593117","NEWT:3635","NEWT:5811","NEWT:235443","NEWT:411483","NEWT:884019","NEWT:198215","NEWT:411490","NEWT:983964","NEWT:169963","NEWT:499175","NEWT:476272","NEWT:3747","NEWT:367830","NEWT:178616","NEWT:410289","NEWT:373153","NEWT:352472","NEWT:360094","NEWT:470","NEWT:1313","NEWT:411469","NEWT:84023","NEWT:559292","NCBITaxon:5811","NEWT:411464","NEWT:411460","NEWT:2762","NEWT:1174673","NEWT:562","NEWT:411470","NEWT:33952","NEWT:2094720","NCBITaxon:2697049","NEWT:28038","NEWT:1423","NEWT:4932","NEWT:3603","NEWT:2759","NEWT:3847","NEWT:327159","NEWT:178876","NEWT:327160","NEWT:573","NEWT:9031","NEWT:7091","NEWT:241368","NEWT:42528","NEWT:190802","NEWT:9778","NEWT:150475","NEWT:9417","NEWT:7111","NEWT:347515","NEWT:1216979","NEWT:5180","NEWT:256737","NEWT:115104","NEWT:1081927","NEWT:1238993","NEWT:67825","NEWT:185579","NEWT:13076","NEWT:1249668","NEWT:317","NEWT:7227","NEWT:7469","NEWT:885318","NEWT:9402","NEWT:415540","NEWT:4081","NEWT:554","NEWT:98334","NEWT:426428","NEWT:7574","NEWT:7215","NEWT:575412","NEWT:29204","NEWT:2172103","NEWT:507601","NCBITaxon:6157","NEWT:746360","NEWT:6239","NEWT:470150","NEWT:216257","NEWT:9986","NEWT:4054","NEWT:73239","NEWT:226186","NEWT:1268063","NEWT:8782","NEWT:1263854","NEWT:435590","NEWT:1902","NEWT:160488","NEWT:28104","NCBITaxon:2","NEWT:985076","NEWT:1215323","NEWT:52641","NEWT:7038","NEWT:6192","NEWT:28532","NCBITaxon:38727","NEWT:2829","NEWT:216599","NEWT:216595","NEWT:243230","NEWT:8355","NEWT:9685","NEWT:7029","NEWT:1080772","NEWT:1283300","NEWT:6183","NEWT:6063","NEWT:334747","NEWT:61235","NEWT:6289","NEWT:436486","NEWT:6287","NEWT:300641","NEWT:727","NEWT:9796","NEWT:725","NEWT:170187","NEWT:260707","NCBITaxon:6191","NEWT:1836","NEWT:185431","NEWT:29760","NEWT:260704","NEWT:703612","NEWT:260705","NEWT:80863","NEWT:2697049","NCBITaxon:6073","NEWT:884204","NEWT:6279","NEWT:1123869","NEWT:9544","NEWT:7370","NEWT:83906","NEWT:607699","NEWT:6282","NEWT:208964","NEWT:1134506","NEWT:575584","NEWT:38783","NEWT:8727","NEWT:4006","NEWT:8726","NEWT:6426","NEWT:6669","NEWT:10090","NEWT:4120","NEWT:51515","NEWT:5693","NEWT:8724","NEWT:51511","NEWT:92867","NEWT:8723","NEWT:5334","NEWT:37334","NEWT:382352","NCBITaxon:10359","NEWT:242619","NEWT:632957","NEWT:373995","NEWT:5689","NEWT:544404","NEWT:9925","NEWT:8839","NEWT:4232","NEWT:2758385","NEWT:4113","NEWT:837","NEWT:11298","NEWT:171101","NEWT:714","NEWT:421932","NEWT:196627","NEWT:5691","NEWT:48479","NEWT:627025","NEWT:1097677","NEWT:61674","NEWT:1117957","NEWT:9913","NEWT:4100","NEWT:1076","NEWT:6763","NEWT:803","NEWT:29722","NEWT:380394","NEWT:1692259","NEWT:180066","NEWT:135588","NEWT:1843183","NEWT:58002","NEWT:326423","NEWT:4577","NEWT:1416333","NEWT:5664","NEWT:2157","NEWT:418985","NEWT:146479","NEWT:1911079","NEWT:264203","NEWT:1480154","NEWT:1274414","NEWT:27606","NEWT:59202","NEWT:9975","NEWT:9612","NEWT:38865","NEWT:51953","NEWT:3197","NEWT:9615","NEWT:10299","NEWT:860688","NEWT:36329","NEWT:1147787","NCBITaxon:3044782","NEWT:72407","NEWT:349741","NEWT:9605","NEWT:9606","NEWT:157295","NEWT:641501","NEWT:7668","NEWT:915099","NEWT:74940","NEWT:9721","NEWT:137221","NEWT:1450511","NEWT:1143193","NEWT:411901","NEWT:9838","NEWT:105884","NCBITaxon:9615","NEWT:58334","NEWT:1193501","NEWT:3055","NEWT:6326","NEWT:6689","NEWT:5476","NEWT:1274432","NEWT:1274426","NEWT:70448","NEWT:9825","NEWT:1274423","NEWT:393765","NEWT:698936","NEWT:39946","NEWT:9823","NEWT:9940","NEWT:521001","NEWT:39947","NEWT:1274420","NEWT:578458"],"pubmed":["42231420"]}}