dc.contributor.author | Haq, N | |
dc.contributor.author | Schmidt-Hieber, C | |
dc.contributor.author | Sialana, FJ | |
dc.contributor.author | Ciani, L | |
dc.contributor.author | Heller, JP | |
dc.contributor.author | Stewart, M | |
dc.contributor.author | Bentley, L | |
dc.contributor.author | Wells, S | |
dc.contributor.author | Rodenburg, RJ | |
dc.contributor.author | Nolan, PM | |
dc.contributor.author | Forsythe, E | |
dc.contributor.author | Wu, MC | |
dc.contributor.author | Lubec, G | |
dc.contributor.author | Salinas, P | |
dc.contributor.author | Häusser, M | |
dc.contributor.author | Beales, PL | |
dc.contributor.author | Christou-Savina, S | |
dc.contributor.editor | Berbari NF | |
dc.coverage.spatial | United States | |
dc.date.accessioned | 2023-07-12T09:08:33Z | |
dc.date.available | 2023-07-12T09:08:33Z | |
dc.date.issued | 2019-09-01 | |
dc.identifier | ARTN e3000414 | |
dc.identifier | PBIOLOGY-D-19-00769 | |
dc.identifier.citation | PLoS Biology, 2019, 17 (9), pp. e3000414 - | en_US |
dc.identifier.issn | 1544-9173 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/5889 | |
dc.identifier.eissn | 1545-7885 | |
dc.identifier.eissn | 1545-7885 | |
dc.identifier.doi | 10.1371/journal.pbio.3000414 | |
dc.description.abstract | Bardet-Biedl syndrome (BBS), a ciliopathy, is a rare genetic condition characterised by retinal degeneration, obesity, kidney failure, and cognitive impairment. In spite of progress made in our general understanding of BBS aetiology, the molecular and cellular mechanisms underlying cognitive impairment in BBS remain elusive. Here, we report that the loss of BBS proteins causes synaptic dysfunction in principal neurons, providing a possible explanation for the cognitive impairment phenotype observed in BBS patients. Using synaptosomal proteomics and immunocytochemistry, we demonstrate the presence of Bbs proteins in the postsynaptic density (PSD) of hippocampal neurons. Loss of Bbs results in a significant reduction of dendritic spines in principal neurons of Bbs mouse models. Furthermore, we show that spine deficiency correlates with events that destabilise spine architecture, such as impaired spine membrane receptor signalling, known to be involved in the maintenance of dendritic spines. Our findings suggest a role for BBS proteins in dendritic spine homeostasis that may be linked to the cognitive phenotype observed in BBS. | |
dc.format | Electronic-eCollection | |
dc.format.extent | e3000414 - | |
dc.language | eng | |
dc.language.iso | eng | en_US |
dc.publisher | PUBLIC LIBRARY SCIENCE | en_US |
dc.relation.ispartof | PLoS Biology | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | en_US |
dc.subject | Animals | |
dc.subject | Anxiety | |
dc.subject | Bardet-Biedl Syndrome | |
dc.subject | Cytoskeletal Proteins | |
dc.subject | Dendritic Spines | |
dc.subject | Dentate Gyrus | |
dc.subject | Disease Models, Animal | |
dc.subject | Excitatory Postsynaptic Potentials | |
dc.subject | Female | |
dc.subject | Male | |
dc.subject | Memory | |
dc.subject | Mice | |
dc.subject | Receptor, IGF Type 1 | |
dc.subject | Synaptosomes | |
dc.title | Loss of Bardet-Biedl syndrome proteins causes synaptic aberrations in principal neurons. | en_US |
dc.type | Journal Article | |
dcterms.dateAccepted | 2019-08-19 | |
dc.date.updated | 2023-07-11T12:46:45Z | |
rioxxterms.version | VoR | en_US |
rioxxterms.versionofrecord | 10.1371/journal.pbio.3000414 | en_US |
rioxxterms.licenseref.startdate | 2019-09-01 | |
rioxxterms.type | Journal Article/Review | en_US |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/31479441 | |
pubs.issue | 9 | |
pubs.organisational-group | /ICR | |
pubs.publication-status | Published online | |
pubs.publisher-url | http://dx.doi.org/10.1371/journal.pbio.3000414 | |
pubs.volume | 17 | |
icr.researchteam | Prote & Metabolomics Fac | en_US |
dc.contributor.icrauthor | Sialana, Fernando Jr | |
icr.provenance | Deposited by Dr Fernando Jr Sialana on 2023-07-11. Deposit type is initial. No. of files: 1. Files: Loss of Bardet-Biedl syndrome proteins causes synaptic aberrations in principal neurons.pdf | |