title: Palmitoylation of δ-catenin by DHHC5 mediates activity-induced synapse plasticity.
abstract: Synaptic cadherin adhesion complexes are known to be key regulators of synapse plasticity. However, the molecular mechanisms that coordinate activity-induced modifications in cadherin localization and adhesion and the subsequent changes in synapse morphology and efficacy remain unknown. We demonstrate that the intracellular cadherin binding protein δ-catenin is transiently palmitoylated by DHHC5 after enhanced synaptic activity and that palmitoylation increases δ-catenin-cadherin interactions at synapses. Both the palmitoylation of δ-catenin and its binding to cadherin are required for activity-induced stabilization of N-cadherin at synapses and the enlargement of postsynaptic spines, as well as the insertion of GluA1 and GluA2 subunits into the synaptic membrane and the concomitant increase in miniature excitatory postsynaptic current amplitude. Notably, context-dependent fear conditioning in mice resulted in increased δ-catenin palmitoylation, as well as increased δ-catenin-cadherin associations at hippocampal synapses. Together these findings suggest a role for palmitoylated δ-catenin in coordinating activity-dependent changes in synaptic adhesion molecules, synapse structure and receptor localization that are involved in memory formation.
authors.affiliation: 1] Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, British Columbia, Canada. [2] Brain Research Centre, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: G Stefano
authors.initials: GS
authors.lastname: Brigidi
authors.affiliation: 1] Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, British Columbia, Canada. [2] Brain Research Centre, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Yu
authors.initials: Y
authors.lastname: Sun
authors.affiliation: 1] Brain Research Centre, University of British Columbia, Vancouver, British Columbia, Canada. [2] Centre for Applied Neurogenetics, Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Dayne
authors.initials: D
authors.lastname: Beccano-Kelly
authors.affiliation: 1] Brain Research Centre, University of British Columbia, Vancouver, British Columbia, Canada. [2] Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Kimberley
authors.initials: K
authors.lastname: Pitman
authors.affiliation: 1] Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, British Columbia, Canada. [2] Brain Research Centre, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Mahsan
authors.initials: M
authors.lastname: Mobasser
authors.affiliation: 1] Brain Research Centre, University of British Columbia, Vancouver, British Columbia, Canada. [2] Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Borgland
authors.affiliation: 1] Brain Research Centre, University of British Columbia, Vancouver, British Columbia, Canada. [2] Centre for Applied Neurogenetics, Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada. [3] Division of Neurology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Austen J
authors.initials: AJ
authors.lastname: Milnerwood
authors.affiliation: 1] Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, British Columbia, Canada. [2] Brain Research Centre, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Shernaz X
authors.initials: SX
authors.lastname: Bamji
mesh_terms: D000217:Acyltransferases; D000818:Animals; D051177:Catenins / Q000378:metabolism / Q000502:physiology*; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D054878:Lipoylation / Q000502:physiology*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008568:Memory / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000378:metabolism / Q000502:physiology*; D013570:Synaptic Membranes / Q000378:metabolism / Q000502:physiology; D000095002:Delta Catenin
chemical_list: D051177:Catenins; D008565:Membrane Proteins; D000217:Acyltransferases; C549503:DHHC5 protein, mouse; D000095002:Delta Catenin