Loss of Bardet-Biedl syndrome proteins causes synaptic aberrations in principal neurons

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Haq, Naila | Schmidt-Hieber, Christoph | Sialana, Fernando, J | Ciani, Lorenza | Heller, Janosch | Stewart, Michelle | Bentley, Liz | Wells, Sara | Rodenburg, Richard | Nolan, Patrick, M | Forsythe, Elizabeth | Wu, Michael | Lubec, Gert | Salinas, P. | Häusser, Michael | Beales, Philip, L | Christou-Savina, Sofia

Edité par CCSD ; Public Library of Science -

International audience. Bardet-Biedl syndrome (BBS), a ciliopathy, is a rare genetic condition characterised by reti-nal 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 synap-tosomal 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.

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