caa a22 4500 606175628 CHVBK 20210128100743.0 cr unu---uuuuu 210128e20150601xx s 000 0 eng 10.1007/s00018-015-1838-x doi (NATIONALLICENCE)springer-10.1007/s00018-015-1838-x Protein composition and movements of membrane swellings associated with primary cilia [Elektronische Daten] [Ashraf Mohieldin, Hanan Haymour, Shao Lo, Wissam AbouAlaiwi, Kimberly Atkinson, Christopher Ward, Min Gao, Oliver Wessely, Surya Nauli] Dysfunction of many ciliary proteins has been linked to a list of diseases, from cystic kidney to obesity and from hypertension to mental retardation. We previously proposed that primary cilia are unique communication organelles that function as microsensory compartments that house mechanosensory molecules. Here we report that primary cilia exhibit membrane swellingsor ciliary bulbs, which based on their unique ultrastructure and motility, could be mechanically regulated by fluid-shear stress. Together with the ultrastructure analysis of the swelling, which contains monosialodihexosylganglioside (GM3), our results show that ciliarybulb has a distinctive set of functional proteins, including GM3 synthase (GM3S), bicaudal-c1 (Bicc1), and polycystin-2 (PC2). In fact, results from our cilia isolation demonstrated for the first time that GM3S and Bicc1 are members of the primary cilia proteins. Although these proteins are not required for ciliary membrane swelling formation under static condition, fluid-shear stress induced swelling formation is partially modulated by GM3S. We therefore propose that the ciliarybulb exhibits a sensory function within the mechano-ciliary structure. Overall, our studies provided an important step towards understanding the ciliarybulb function and structure. Springer Basel, 2015 Primary cilia nationallicence Ciliary bulb nationallicence Ciliary membrane swelling nationallicence Fluid-shear stress nationallicence Bicc-1 nationallicence GM3S nationallicence PC2 nationallicence Mohieldin Ashraf Department of Medicinal and Biological Chemistry, University of Toledo, Health Science Building, 3000 Arlington Ave, 43614, Toledo, OH, USA aut Haymour Hanan Department of Pharmacology and Experimental Therapeutics, University of Toledo, Health Science Building, 43614, Toledo, OH, USA aut Lo Shao Department of Pharmacology and Experimental Therapeutics, University of Toledo, Health Science Building, 43614, Toledo, OH, USA aut AbouAlaiwi Wissam Department of Pharmacology and Experimental Therapeutics, University of Toledo, Health Science Building, 43614, Toledo, OH, USA aut Atkinson Kimberly Department of Biomedical and Pharmaceutical Sciences, Chapman University, Harry and Diane Rinker Health Science Campus, 9401 Jeronimo Road, 92618-1908, Irvine, CA, USA aut Ward Christopher Department of Medicine, The Kidney Institute, University of Kansas Medical Center, 66160, Kansas, KS, USA aut Gao Min Liquid Crystal Institute, Kent State University, 1425 University Esplanade, 44242, Kent, OH, USA aut Wessely Oliver Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic Foundation, 44195, Cleveland, OH, USA aut Nauli Surya Department of Medicinal and Biological Chemistry, University of Toledo, Health Science Building, 3000 Arlington Ave, 43614, Toledo, OH, USA aut Cellular and Molecular Life Sciences Springer Basel 72/12(2015-06-01), 2415-2429 1420-682X 72:12<2415 2015 72 18 https://doi.org/10.1007/s00018-015-1838-x text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00018-015-1838-x text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Mohieldin Ashraf Department of Medicinal and Biological Chemistry, University of Toledo, Health Science Building, 3000 Arlington Ave, 43614, Toledo, OH, USA aut NATIONALLICENCE 700 1- Haymour Hanan Department of Pharmacology and Experimental Therapeutics, University of Toledo, Health Science Building, 43614, Toledo, OH, USA aut NATIONALLICENCE 700 1- Lo Shao Department of Pharmacology and Experimental Therapeutics, University of Toledo, Health Science Building, 43614, Toledo, OH, USA aut NATIONALLICENCE 700 1- AbouAlaiwi Wissam Department of Pharmacology and Experimental Therapeutics, University of Toledo, Health Science Building, 43614, Toledo, OH, USA aut NATIONALLICENCE 700 1- Atkinson Kimberly Department of Biomedical and Pharmaceutical Sciences, Chapman University, Harry and Diane Rinker Health Science Campus, 9401 Jeronimo Road, 92618-1908, Irvine, CA, USA aut NATIONALLICENCE 700 1- Ward Christopher Department of Medicine, The Kidney Institute, University of Kansas Medical Center, 66160, Kansas, KS, USA aut NATIONALLICENCE 700 1- Gao Min Liquid Crystal Institute, Kent State University, 1425 University Esplanade, 44242, Kent, OH, USA aut NATIONALLICENCE 700 1- Wessely Oliver Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic Foundation, 44195, Cleveland, OH, USA aut NATIONALLICENCE 700 1- Nauli Surya Department of Medicinal and Biological Chemistry, University of Toledo, Health Science Building, 3000 Arlington Ave, 43614, Toledo, OH, USA aut NATIONALLICENCE 773 0- Cellular and Molecular Life Sciences Springer Basel 72/12(2015-06-01), 2415-2429 1420-682X 72:12<2415 2015 72 18