{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Hegazi S"],"funding":["Gouvernement du Canada | Natural Sciences and Engineering Research Council of Canada","Gouvernement du Canada | Canadian Institutes of Health Research","CIHR"],"pagination":["1594"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8948264"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["13(1)"],"pubmed_abstract":["Ubiquitin ligases control the degradation of core clock proteins to govern the speed and resetting properties of the circadian pacemaker. However, few studies have addressed their potential to regulate other cellular events within clock neurons beyond clock protein turnover. Here, we report that the ubiquitin ligase, UBR4/POE, strengthens the central pacemaker by facilitating neuropeptide trafficking in clock neurons and promoting network synchrony. Ubr4-deficient mice are resistant to jetlag, whereas poe knockdown flies are prone to arrhythmicity, behaviors reflective of the reduced axonal trafficking of circadian neuropeptides. At the cellular level, Ubr4 ablation impairs the export of secreted proteins from the Golgi apparatus by reducing the expression of Coronin 7, which is required for budding of Golgi-derived transport vesicles. In summary, UBR4/POE fulfills a conserved and unexpected role in the vesicular trafficking of neuropeptides, a function that has important implications for circadian clock synchrony and circuit-level signal processing."],"journal":["Nature communications"],"pubmed_title":["UBR4/POE facilitates secretory trafficking to maintain circadian clock synchrony."],"pmcid":["PMC8948264"],"funding_grant_id":["PJT-175131","RGPIN-2016-05563","RGPIN-2019-06137","PJT-166046","PJT-148679-S","RGPIN-2016-06218","PJ8-162479","MOP-286265, PJT-166046, and PJ8-162479","MOP-286265"],"pubmed_authors":["Cheng HM","Liu J","Cheng AH","Liu BH","Hegazi S","Basiri T","Ahmad S","Levine JD","Tasaki T","Sonenberg N","Ling HH","Krupp JJ","Anwar Z","Amiri M","Rios Garcia J","Szulc DA","Seecharran S","Nayal K"],"additional_accession":[]},"is_claimable":false,"name":"UBR4/POE facilitates secretory trafficking to maintain circadian clock synchrony.","description":"Ubiquitin ligases control the degradation of core clock proteins to govern the speed and resetting properties of the circadian pacemaker. However, few studies have addressed their potential to regulate other cellular events within clock neurons beyond clock protein turnover. Here, we report that the ubiquitin ligase, UBR4/POE, strengthens the central pacemaker by facilitating neuropeptide trafficking in clock neurons and promoting network synchrony. Ubr4-deficient mice are resistant to jetlag, whereas poe knockdown flies are prone to arrhythmicity, behaviors reflective of the reduced axonal trafficking of circadian neuropeptides. At the cellular level, Ubr4 ablation impairs the export of secreted proteins from the Golgi apparatus by reducing the expression of Coronin 7, which is required for budding of Golgi-derived transport vesicles. In summary, UBR4/POE fulfills a conserved and unexpected role in the vesicular trafficking of neuropeptides, a function that has important implications for circadian clock synchrony and circuit-level signal processing.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Mar","modification":"2025-04-04T21:33:35.495Z","creation":"2025-04-04T21:33:35.495Z"},"accession":"S-EPMC8948264","cross_references":{"pubmed":["35332162"],"doi":["10.1038/s41467-022-29244-1"]}}