title: DLG3/SAP102 protein expression in malformations of cortical development: a study of human epileptic cortex by tissue microarray.
abstract: The human DLG3 gene encodes the synapse-associated protein 102 (SAP102), which is concentrated in the postsynaptic densities of excitatory synapses and involved in receptor-mediated synaptic transmission via binding to the NR2B subunit of the NMDA receptor. In this study, we investigated the expression and cellular distribution of the DLG3/SAP102 protein in human epileptic cortex. Tissue microarrays of a large number of specimens from patients operated for medically intractable epilepsy were used for immunohistochemical screening with anti-DLG3 antibody. The cellular distribution of the protein was further investigated in samples of malformations of cortical development, and the amount of DLG3 protein in the total homogenate and in the postsynaptic membrane fraction of these samples was quantified by Western blot. We found a strictly neuronal expression of DLG3/SAP102 in epileptogenic cortex as well as in non-epileptic human cortex used for control. In focal cortical dysplasia and tuberous sclerosis complex, the protein was expressed in most neurons including dysplastic neurons, but not in giant cells. Increased expression of DLG3 protein was observed in the postsynaptic membrane fraction of patients with focal cortical dysplasia. Double-labeling experiments confirmed the exclusive neuronal character of the DLG3 expressing cells and the co-localization of the DLG3 protein with the NR2B subunit. Our results suggest a putative role for DLG3/SAP102 in cortical hyperexcitability and epileptogenicity of malformations of cortical development.
authors.affiliation: Department of Neuroscience, Neurology, Uppsala University Hospital, Sweden.
authors.forename: Mingqi
authors.initials: M
authors.lastname: Qu
authors.forename: Eleonora
authors.initials: E
authors.lastname: Aronica
authors.forename: Karin
authors.initials: K
authors.lastname: Boer
authors.forename: David
authors.initials: D
authors.lastname: Fällmar
authors.forename: Eva
authors.initials: E
authors.lastname: Kumlien
authors.forename: Monica
authors.initials: M
authors.lastname: Nistér
authors.forename: Kenneth
authors.initials: K
authors.lastname: Wester
authors.forename: Fredrik
authors.initials: F
authors.lastname: Pontén
authors.forename: Anja
authors.initials: A
authors.lastname: Smits
mesh_terms: D000328:Adult; D000368:Aged; D034961:Antigens, Nuclear / Q000378:metabolism; D001344:Autopsy / Q000379:methods; D002540:Cerebral Cortex / Q000378:metabolism*; D004827:Epilepsy / Q000473:pathology*; D005260:Female; D015870:Gene Expression / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D008297:Male; D046228:Microarray Analysis / Q000379:methods; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D012189:Retrospective Studies; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D034961:Antigens, Nuclear; C116869:DLG3 protein, human; D005904:Glial Fibrillary Acidic Protein; D008869:Microtubule-Associated Proteins; C409466:NR1 NMDA receptor; C121001:NR2B NMDA receptor; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D016194:Receptors, N-Methyl-D-Aspartate; D014157:Transcription Factors; C506808:neuronal nuclear antigen NeuN, human