The BEACH Protein LRBA Promotes the Localization of the Heterotrimeric G-protein Golf to Olfactory Cilia
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 repor...
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2017
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oai:doaj.org-article:3f19e8543c154b8eb7ffd756b32582572021-12-02T11:40:14ZThe BEACH Protein LRBA Promotes the Localization of the Heterotrimeric G-protein Golf to Olfactory Cilia10.1038/s41598-017-08543-42045-2322https://doaj.org/article/3f19e8543c154b8eb7ffd756b32582572017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08543-4https://doaj.org/toc/2045-2322Abstract 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.Stefan KurtenbachAndreas GießlSiv StrömbergJan KremersJenny AtorfSebastian RascheEva M. NeuhausDenis HervéJohann Helmut BrandstätterEsther AsanHanns HattManfred W. KilimannNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-19 (2017) |
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Medicine R Science Q Stefan Kurtenbach Andreas Gießl Siv Strömberg Jan Kremers Jenny Atorf Sebastian Rasche Eva M. Neuhaus Denis Hervé Johann Helmut Brandstätter Esther Asan Hanns Hatt Manfred W. Kilimann The BEACH Protein LRBA Promotes the Localization of the Heterotrimeric G-protein Golf to Olfactory Cilia |
| description |
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. |
| format |
article |
| author |
Stefan Kurtenbach Andreas Gießl Siv Strömberg Jan Kremers Jenny Atorf Sebastian Rasche Eva M. Neuhaus Denis Hervé Johann Helmut Brandstätter Esther Asan Hanns Hatt Manfred W. Kilimann |
| author_facet |
Stefan Kurtenbach Andreas Gießl Siv Strömberg Jan Kremers Jenny Atorf Sebastian Rasche Eva M. Neuhaus Denis Hervé Johann Helmut Brandstätter Esther Asan Hanns Hatt Manfred W. Kilimann |
| author_sort |
Stefan Kurtenbach |
| title |
The BEACH Protein LRBA Promotes the Localization of the Heterotrimeric G-protein Golf to Olfactory Cilia |
| title_short |
The BEACH Protein LRBA Promotes the Localization of the Heterotrimeric G-protein Golf to Olfactory Cilia |
| title_full |
The BEACH Protein LRBA Promotes the Localization of the Heterotrimeric G-protein Golf to Olfactory Cilia |
| title_fullStr |
The BEACH Protein LRBA Promotes the Localization of the Heterotrimeric G-protein Golf to Olfactory Cilia |
| title_full_unstemmed |
The BEACH Protein LRBA Promotes the Localization of the Heterotrimeric G-protein Golf to Olfactory Cilia |
| title_sort |
beach protein lrba promotes the localization of the heterotrimeric g-protein golf to olfactory cilia |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/3f19e8543c154b8eb7ffd756b3258257 |
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