{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Martin-de-Saavedra MD"],"funding":["NIA NIH HHS","NIMH NIH HHS","NINDS NIH HHS","NCI NIH HHS","NIAMS NIH HHS","NIH HHS"],"pagination":["627-643.e9"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8857041"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["110(4)"],"pubmed_abstract":["Although many neuronal membrane proteins undergo proteolytic cleavage, little is known about the biological significance of neuronal ectodomain shedding (ES). Here, we show that the neuronal sheddome is detectable in human cerebrospinal fluid (hCSF) and is enriched in neurodevelopmental disorder (NDD) risk factors. Among shed synaptic proteins is the ectodomain of CNTNAP2 (CNTNAP2-ecto), a prominent NDD risk factor. CNTNAP2 undergoes activity-dependent ES via MMP9 (matrix metalloprotease 9), and CNTNAP2-ecto levels are reduced in the hCSF of individuals with autism spectrum disorder. Using mass spectrometry, we identified the plasma membrane Ca<sup>2+</sup> ATPase (PMCA) extrusion pumps as novel CNTNAP2-ecto binding partners. CNTNAP2-ecto enhances the activity of PMCA2 and regulates neuron"],"journal":["Neuron"],"pubmed_title":["Shed CNTNAP2 ectodomain is detectable in CSF and regulates Ca<sup>2+</sup> homeostasis and network synchrony via PMCA2/ATP2B2."],"pmcid":["PMC8857041"],"funding_grant_id":["R01 MH107182","R56 NS100785","P30 AR075049","R01 MH097216","S10 OD016342","P30 CA060553","R01 AG069266","R01 NS100785","R01 MH092906"],"pubmed_authors":["McCoig E","Varea O","Burgdorf JS","Yoon S","Turk LS","Hall EA","Martin-de-Saavedra MD","Comoletti D","Culotta L","Parnell E","Savas JN","Lichtenthaler SF","Penzes P","Gao R","Khalatyan N","Dos Santos M","Forrest MP","Myczek K","Sanz-Clemente A","Spielman BP","Jalloul HA","Barbolina MV"],"additional_accession":[]},"is_claimable":false,"name":"Shed CNTNAP2 ectodomain is detectable in CSF and regulates Ca<sup>2+</sup> homeostasis and network synchrony via PMCA2/ATP2B2.","description":"Although many neuronal membrane proteins undergo proteolytic cleavage, little is known about the biological significance of neuronal ectodomain shedding (ES). Here, we show that the neuronal sheddome is detectable in human cerebrospinal fluid (hCSF) and is enriched in neurodevelopmental disorder (NDD) risk factors. Among shed synaptic proteins is the ectodomain of CNTNAP2 (CNTNAP2-ecto), a prominent NDD risk factor. CNTNAP2 undergoes activity-dependent ES via MMP9 (matrix metalloprotease 9), and CNTNAP2-ecto levels are reduced in the hCSF of individuals with autism spectrum disorder. Using mass spectrometry, we identified the plasma membrane Ca<sup>2+</sup> ATPase (PMCA) extrusion pumps as novel CNTNAP2-ecto binding partners. CNTNAP2-ecto enhances the activity of PMCA2 and regulates neuron","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Feb","modification":"2026-05-08T19:57:11.167Z","creation":"2025-02-19T03:26:56.905Z"},"accession":"S-EPMC8857041","cross_references":{"pubmed":["34921780"],"doi":["10.1016/j.neuron.2021.11.025"]}}