ArticleNeuron2022
Shed CNTNAP2 ectodomain is detectable in CSF and regulates Ca
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Article in Neuron, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 41 citations in OpenAlex.
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- CNTNAP2: isoform- and context-specific functions in neurological disorders and cancer.Frontiers in cellular neuroscience · 2026Review
- Shared Disease Mechanisms in Neurodevelopmental Disorders: A Cellular and Molecular Biology Perspective.Brain sciences · 2025Review
- Calcium Dynamics in Astrocyte-Neuron Communication from Intracellular to Extracellular Signaling.Cells · 2025Review
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- Developmental and Epileptic Encephalopathy: Pathogenesis of Intellectual Disability Beyond Channelopathies.Biomolecules · 2025Review
- Single-nucleotide polymorphism analysis accurately predicts multiple impairments in hippocampal activity and memory performance in a murine model of idiopathic autism.Scientific reports · 2025Article
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- Soluble form of Lingo2, an autism spectrum disorder-associated molecule, functions as an excitatory synapse organizer in neurons.Translational psychiatry · 2024Article
- Neurogenetic underpinnings of nicotine use severity: Integrating the brain transcriptomes and GWAS variants via network approaches.Psychiatry research · 2024Article
- Contactin-associated protein-like 2 (CNTNAP2) mutations impair the essential α-secretase cleavages, leading to autism-like phenotypes.Signal transduction and targeted therapy · 2024Article
- Ultrahigh frequencies of peripherally matured LGI1- and CASPR2-reactive B cells characterize the cerebrospinal fluid in autoimmune encephalitis.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- iPSC-derived models of PACS1 syndrome reveal transcriptional and functional deficits in neuron activity.Nature communications · 2024Article
- TDP-43-stratified single-cell proteomics of postmortem human spinal motor neurons reveals protein dynamics in amyotrophic lateral sclerosis.Cell reports · 2024Article
- A methodology to globally assess ectodomain shedding using soluble fractions from the mouse brain.Frontiers in psychiatry · 2024Article
- Low Plasma Levels of Contactin-Associated Protein-Like 2 in Children with Autism Spectrum Disorder: Links to Neural Development.Neuropsychiatric disease and treatment · 2024Article
- CNTNAP2 intracellular domain (CICD) generated by γ-secretase cleavage improves autism-related behaviors.Signal transduction and targeted therapy · 2023Article
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Authors and funding
22 authors at 4 institutions in 2 countries.
M Dolores Martín-de-SaavedraDepartment of Physiology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Marc Dos SantosDepartment of Physiology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Lorenza CulottaDepartment of Physiology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Olga VareaDepartment of Physiology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Benjamin P SpielmanDepartment of Physiology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Euan ParnellDepartment of Physiology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Marc P ForrestDepartment of Physiology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Ruoqi GaoDepartment of Physiology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Sehyoun YoonDepartment of Physiology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Emmarose McCoigDepartment of Physiology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Hiba A JalloulDepartment of Physiology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Kristoffer MyczekDepartment of Physiology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Natalia KhalatyanDepartment of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Elizabeth A HallDepartment of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Liam S TurkChild Health Institute of New Jersey, New Brunswick, NJ 08901, USA; Department of Neuroscience and Cell Biology, Robert Wood Johnson Medical School, Rutgers, the State University of New Jersey, New Brunswick, NJ 08901, USA.
Antonio Sanz-ClementeDepartment of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Davide ComolettiChild Health Institute of New Jersey, New Brunswick, NJ 08901, USA; Department of Neuroscience and Cell Biology, Robert Wood Johnson Medical School, Rutgers, the State University of New Jersey, New Brunswick, NJ 08901, USA; Department of Pediatrics, Robert Wood Johnson Medical School, Rutgers, the State University of New Jersey, New Brunswick, NJ 08901, USA; School of Biological Sciences, Victoria University of Wellington, Wellington 6140, New Zealand.
Stefan F LichtenthalerGerman Center for Neurodegenerative Diseases (DZNE), 81377 Munich, Germany; Department of Neuroproteomics, School of Medicine, Klinikum rechts der Isar, and Institute for Advanced Study, Technical University of Munich, 81675 Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), 81377 Munich, Germany.
Jeffrey S BurgdorfDepartment of Physiology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA; Center for Autism and Neurodevelopment, Northwestern University, Chicago, IL 60611, USA; Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Maria V BarbolinaDepartment of Biopharmaceutical Sciences, University of Illinois at Chicago, Chicago, IL 60607, USA.
Jeffrey N SavasDepartment of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Peter PenzesDepartment of Physiology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA; Center for Autism and Neurodevelopment, Northwestern University, Chicago, IL 60611, USA; Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA. Electronic address: p-penzes@northwestern.edu.
Northwestern University · USRutgers, The State University of New Jersey · USGerman Center for Neurodegenerative Diseases · DEUniversity of Illinois Chicago · US
Funding
Tumor Environment and Metastasis (TEAM) Research ProgramP30CA060553 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Daniela E Matei · 1993 to 2026
$153.9MNorthwestern University Skin Disease Research Center Resource-based CenterP30AR075049 · NIAMS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Amy S Paller · 2019 to 2026
$6.6MSynaptic and dendritic dysfunction in psychiatric disordersR01MH097216 · NIMH · NORTHWESTERN UNIVERSITY AT CHICAGO · PI PENZES, PETER · 2012 to 2021
$6.1MPostsynaptic roles of ankyrinsR01MH107182 · NIMH · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Peter Penzes · 2015 to 2026
$5.6MExploring the modulation of synaptic/extrasynaptic NMDAR balance as a novel therapeutic strategy in Alzheimer's disease and other neurodegenerationsR01AG069266 · NIA · NORTHWESTERN UNIVERSITY AT CHICAGO · PI SANZ-CLEMENTE, ANTONIO · 2020 to 2024
$2.4MPostsynaptic functions of neuronal adhesion molecules: focus on Cntnap2R01NS100785 · NINDS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI PENZES, PETER · 2017 to 2020
$2.0MCaspr2 as an autism candidate gene: a proteomic approach to function & structure.R01MH092906 · NIMH · UNIV OF MED/DENT NJ-R W JOHNSON MED SCH · PI COMOLETTI, DAVIDE · 2011 to 2015
$1.6MNikon Super-Resolution Structured Illumination Microscope (SIM)S10OD016342 · OD · NORTHWESTERN UNIVERSITY AT CHICAGO · PI CHEW, TENG-LEONG · 2013 to 2013
$600kAdhesion molecules and developmental epilepsy disordersR56NS100785 · NINDS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI PENZES, PETER · 2022 to 2022
$545kNCI NIH HHS P30 CA060553NIAMS NIH HHS P30 AR075049NIA NIH HHS R01 AG069266NIH HHS S10 OD016342NIMH NIH HHS R01 MH092906NIMH NIH HHS R01 MH097216NIMH NIH HHS R01 MH107182NINDS NIH HHS R01 NS100785NINDS NIH HHS R56 NS100785
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
Indexed as
Autism Spectrum DisorderMembrane ProteinsNerve Tissue ProteinsPlasma Membrane Calcium-Transporting ATPasesCell MembraneHomeostasisHumansNeuronsSignal TransductionATP2B2 protein, humanCNTNAP2 protein, humanMembrane ProteinsNerve Tissue ProteinsPlasma Membrane Calcium-Transporting ATPasesautismbioinformaticscalciumcerebrospinal fluidCNTNAP2ectodomain sheddingnetwork dynamicsproteomicsschizophreniasheddome
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