The CNTNAP2-CASK complex modulates GluA1 subcellular distribution in interneurons

Publication date: Available online 16 February 2019Source: Neuroscience LettersAuthor(s): Ruoqi Gao, Colleen R. Zaccard, Lauren P. Shapiro, Leonardo E. Dionisio, Maria Dolores Martin-de-Saavedra, Nicolas H. Piguel, Christopher P. Pratt, Katherine E. Horan, Peter PenzesAbstractGABAergic interneurons are emerging as prominent substrates in the pathophysiology of multiple neurodevelopmental disorders, including autism spectrum disorders, schizophrenia, intellectual disability, and epilepsy. Interneuron excitatory activity is influenced by 2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl) propanoic acid receptors (AMPARs), which in turn affects excitatory transmission in the central nervous system. Yet how dysregulation of interneuronal AMPARs distinctly contributes to the molecular underpinning of neurobiological disease is drastically underexplored. Contactin-associated protein-like 2 (CNTNAP2) is a neurexin-related adhesion molecule shown to mediate AMPAR subcellular distribution while calcium/calmodulin-dependent serine protein kinase (CASK) is a multi-functional scaffold involved with glutamate receptor trafficking. Mutations in both genes have overlapping disease associations, including autism spectrum disorders, intellectual disability, and epilepsy, thus suggesting converging perturbations of excitatory/inhibitory balance. Our lab has previously shown that CNTNAP2 stabilizes interneuron dendritic arbors through CASK and that CNTNAP2 regulates AMPAR subunit GluA1 trafficking in...
Source: Neuroscience Letters - Category: Neuroscience Source Type: research