The female epilepsy protein PCDH19 is a new GABAAR-binding partner that regulates GABAergic transmission as well as migration and morphological maturation of hippocampal neurons | Zendy

Silvia Bassani | Zendy; Andrzej Cwetsch | Zendy; Laura Gerosa | Zendy; Giulia Maia Serratto | Zendy; Alessandra Folci | Zendy; Ignacio Fernando Hall | Zendy; Michele Mazzanti | Zendy; Laura Cancedda | Zendy; Maria Passafaro | Zendy

Open Access

The female epilepsy protein PCDH19 is a new GABAAR-binding partner that regulates GABAergic transmission as well as migration and morphological maturation of hippocampal neurons

Author(s) -

Silvia Bassani,

Andrzej Cwetsch,

Laura Gerosa,

Giulia Maia Serratto,

Alessandra Folci,

Ignacio Fernando Hall,

Michele Mazzanti,

Laura Cancedda,

Maria Passafaro

Publication year - 2018

Publication title -

human molecular genetics

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.811

H-Index - 276

eISSN - 1460-2083

pISSN - 0964-6906

DOI - 10.1093/hmg/ddy019

Subject(s) - biology , hippocampal formation , gabaa receptor , downregulation and upregulation , gabaergic , neuroscience , protocadherin , inhibitory postsynaptic potential , microbiology and biotechnology , gephyrin , postsynaptic potential , epilepsy , neurotransmission , hippocampus , receptor , gene , genetics , cell , cadherin , glycine , glycine receptor , amino acid

The PCDH19 gene (Xp22.1) encodes the cell-adhesion protein protocadherin-19 (PCDH19) and is responsible for a neurodevelopmental pathology characterized by female-limited epilepsy, cognitive impairment and autistic features, the pathogenic mechanisms of which remain to be elucidated. Here, we identified a new interaction between PCDH19 and GABAA receptor (GABAAR) alpha subunits in the rat brain. PCDH19 shRNA-mediated downregulation reduces GABAAR surface expression and affects the frequency and kinetics of miniature inhibitory postsynaptic currents (mIPSCs) in cultured hippocampal neurons. In vivo, PCDH19 downregulation impairs migration, orientation and dendritic arborization of CA1 hippocampal neurons and increases rat seizure susceptibility. In sum, these data indicate a role for PCDH19 in GABAergic transmission as well as migration and morphological maturation of neurons.

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