{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Xu ZX"],"funding":["NIDA NIH HHS","NIDDK NIH HHS","NIMH NIH HHS","NINDS NIH HHS","U.S. Department of Health & Human Services | National Institutes of Health"],"pagination":["3622"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6689033"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["10(1)"],"pubmed_abstract":["Caspase-2 is the most evolutionarily conserved member in the caspase family of proteases and is constitutively expressed in most cell types including neurons; however, its physiological function remains largely unknown. Here we report that caspase-2 plays a critical role in synaptic plasticity and cognitive flexibility. We found that caspase-2 deficiency led to deficits in dendritic spine pruning, internalization of AMPA receptors and long-term depression. Our results indicate that caspase-2 degrades Rictor, a key mTOR complex 2 (mTORC2) component, to inhibit Akt activation, which leads to enhancement of the GSK3β activity and thereby long-term depression. Furthermore, we found that mice lacking caspase-2 displayed elevated levels of anxiety, impairment in reversal water maze learning, and"],"journal":["Nature communications"],"pubmed_title":["Caspase-2 promotes AMPA receptor internalization and cognitive flexibility via mTORC2-AKT-GSK3β signaling."],"pmcid":["PMC6689033"],"funding_grant_id":["R01 NS073930","DK103335","R01 DK105954","MH105482","R01 DK103335","DK105954","NS073930","R01 MH105482","K02 DA026405"],"pubmed_authors":["Martemyanov KA","Xu B","Hill CJ","Xu ZX","Tan JW","Xu H","Ostrovskaya O"],"additional_accession":[]},"is_claimable":false,"name":"Caspase-2 promotes AMPA receptor internalization and cognitive flexibility via mTORC2-AKT-GSK3β signaling.","description":"Caspase-2 is the most evolutionarily conserved member in the caspase family of proteases and is constitutively expressed in most cell types including neurons; however, its physiological function remains largely unknown. Here we report that caspase-2 plays a critical role in synaptic plasticity and cognitive flexibility. We found that caspase-2 deficiency led to deficits in dendritic spine pruning, internalization of AMPA receptors and long-term depression. Our results indicate that caspase-2 degrades Rictor, a key mTOR complex 2 (mTORC2) component, to inhibit Akt activation, which leads to enhancement of the GSK3β activity and thereby long-term depression. Furthermore, we found that mice lacking caspase-2 displayed elevated levels of anxiety, impairment in reversal water maze learning, and","dates":{"release":"2019-01-01T00:00:00Z","publication":"2019 Aug","modification":"2025-04-29T11:06:03.077Z","creation":"2019-08-16T07:02:27Z"},"accession":"S-EPMC6689033","cross_references":{"pubmed":["31399584"],"doi":["10.1038/s41467-019-11575-1"]}}