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Sci Rep. 2017 Aug 16;7(1):8409. doi: 10.1038/s41598-017-08543-4.

The BEACH Protein LRBA Promotes the Localization of the Heterotrimeric G-protein Golf to Olfactory Cilia.

Author information

1
Department of Cell Physiology, Ruhr University Bochum, D-44780, Bochum, Germany.
2
Department of Biology, Animal Physiology, University of Erlangen-Nürnberg, D-91058, Erlangen, Germany.
3
Department of Neuroscience, Uppsala University, S-75124, Uppsala, Sweden.
4
Department of Ophthalmology, University Hospital Erlangen, D-91054, Erlangen, Germany.
5
Department of Anatomy II, Friedrich-Alexander University Erlangen-Nürnberg, D-91054, Erlangen, Germany.
6
Department of Pharmacology and Toxikology, University Hospital Jena, D-07747, Jena, Germany.
7
Inserm UMR-S839, Institut du Fer a Moulin, Universite Pierre et Marie Curie, F-75005, Paris, France.
8
Institute of Anatomy and Cell Biology, University of Würzburg, D-97070, Würzburg, Germany.
9
Department of Neuroscience, Uppsala University, S-75124, Uppsala, Sweden. Kilimann@em.mpg.de.
10
Department of Molecular Neurobiology, Max Planck Institute for Experimental Medicine, D-37075, Göttingen, Germany. Kilimann@em.mpg.de.

Abstract

BEACH domain proteins are involved in membrane protein traffic and human diseases, but their molecular mechanisms are not understood. The BEACH protein LRBA has been implicated in immune response and cell proliferation, and human LRBA mutations cause severe immune deficiency. Here, we report a first functional and molecular phenotype outside the immune system of LRBA-knockout mice: compromised olfaction, manifesting in reduced electro-olfactogram response amplitude, impaired food-finding efficiency, and smaller olfactory bulbs. LRBA is prominently expressed in olfactory and vomeronasal chemosensory neurons of wild-type mice. Olfactory impairment in the LRBA-KO is explained by markedly reduced concentrations (20-40% of wild-type levels) of all three subunits αolf, β1 and γ13 of the olfactory heterotrimeric G-protein, Golf, in the sensory cilia of olfactory neurons. In contrast, cilia morphology and the concentrations of many other proteins of olfactory cilia are not or only slightly affected. LRBA is also highly expressed in photoreceptor cells, another cell type with a specialized sensory cilium and heterotrimeric G-protein-based signalling; however, visual function appeared unimpaired by the LRBA-KO. To our knowledge, this is the first observation that a BEACH protein is required for the efficient subcellular localization of a lipid-anchored protein, and of a ciliary protein.

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