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  Epilepsy and intellectual disability linked protein Shrm4 interaction with GABABRs shapes inhibitory neurotransmission

Zapata, J., Moretto, E., Hannan, S., Murru, L., Longatti, A., Mazza, D., et al. (2017). Epilepsy and intellectual disability linked protein Shrm4 interaction with GABABRs shapes inhibitory neurotransmission. Nature Communications, 8: 8:14536. doi:10.1038/ncomms14536.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0000-CDCB-5 Version Permalink: http://hdl.handle.net/21.11116/0000-0000-CDCC-4
Genre: Journal Article

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 Creators:
Zapata, J., Author
Moretto, E., Author
Hannan, S., Author
Murru, L., Author
Longatti, A., Author
Mazza, D., Author
Benedetti, L., Author
Fossati, M., Author
Heise, C., Author
Ponzoni, L., Author
Valnegri, P., Author
Braida, D., Author
Sala, M., Author
Francolini, M., Author
Hildebrand, J., Author
Kalscheuer, V.1, Author              
Fanelli, F., Author
Sala, C., Author
Bettler, B., Author
Bassani, S., Author
Smart, T. G., AuthorPassafaro, M., Author more..
Affiliations:
1Chromosome Rearrangements and Disease (Vera Kalscheuer), Research Group Development & Disease (Head: Stefan Mundlos), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_2385702              

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 Abstract: Shrm4, a protein expressed only in polarized tissues, is encoded by the KIAA1202 gene, whose mutations have been linked to epilepsy and intellectual disability. However, a physiological role for Shrm4 in the brain is yet to be established. Here, we report that Shrm4 is localized to synapses where it regulates dendritic spine morphology and interacts with the C terminus of GABAB receptors (GABABRs) to control their cell surface expression and intracellular trafficking via a dynein-dependent mechanism. Knockdown of Shrm4 in rat severely impairs GABABR activity causing increased anxiety-like behaviour and susceptibility to seizures. Moreover, Shrm4 influences hippocampal excitability by modulating tonic inhibition in dentate gyrus granule cells, in a process involving crosstalk between GABABRs and extrasynaptic delta-subunit-containing GABAARs. Our data highlights a role for Shrm4 in synaptogenesis and in maintaining GABABR-mediated inhibition, perturbation of which may be responsible for the involvement of Shrm4 in cognitive disorders and epilepsy.

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Language(s): eng - English
 Dates: 2017-01-092017-03-06
 Publication Status: Published online
 Pages: -
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 Table of Contents: -
 Rev. Method: -
 Identifiers: DOI: 10.1038/ncomms14536
ISSN: 2041-1723 (Electronic)
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Title: Nature Communications
  Abbreviation : Nat. Commun.
Source Genre: Journal
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Publ. Info: London : Nature Publishing Group
Pages: - Volume / Issue: 8 Sequence Number: 8:14536 Start / End Page: - Identifier: ISSN: 2041-1723
CoNE: /journals/resource/2041-1723