title: Protein composition and movements of membrane swellings associated with primary cilia.
abstract: 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 swellings or 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 ciliary bulb 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 ciliary bulb exhibits a sensory function within the mechano-ciliary structure. Overall, our studies provided an important step towards understanding the ciliary bulb function and structure.
authors: Department of Medicinal and Biological Chemistry, University of Toledo, Health Science Building, 3000 Arlington Ave, Toledo, OH, 43614, USA, Ashraf.Mohieldin@rockets.utoledo.edu.
authors: Ashraf M
authors: AM
authors: Mohieldin
authors: Hanan S
authors: HS
authors: Haymour
authors: Shao T
authors: ST
authors: Lo
authors: Wissam A
authors: WA
authors: AbouAlaiwi
authors: Kimberly F
authors: KF
authors: Atkinson
authors: Christopher J
authors: CJ
authors: Ward
authors: Min
authors: M
authors: Gao
authors: Oliver
authors: O
authors: Wessely
authors: Surya M
authors: SM
authors: Nauli
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000502:physiology*; D002923:Cilia / Q000502:physiology*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D007091:Image Processing, Computer-Assisted; D015151:Immunoblotting; D007668:Kidney / Q000166:cytology / Q000378:metabolism*; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D034741:RNA, Small Interfering / Q000235:genetics; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012799:Sialyltransferases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D013552:Swine; D050396:TRPP Cation Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D050396:TRPP Cation Channels; D012799:Sialyltransferases; C021343:haematoside synthetase
references: Circulation. 2014 Feb 11;129(6):660-72
references: 24235270
references: Curr Protoc Cell Biol. 2013 Jun;Chapter 3:3.42.1-3.42.9
references: 23728745
references: Biol Bull. 1991 Jun;180(3):466-474
references: 29304655
references: J Cell Sci. 1988 Apr;89 ( Pt 4):457-66
references: 3058727
references: Circulation. 2008 Mar 4;117(9):1161-71
references: 18285569
references: Biol Sci Space. 2004 Nov;18(3):181-2
references: 15858381
references: Nat Methods. 2013 Nov;10(11):1105-7
references: 24056873
references: Am J Physiol Renal Physiol. 2006 Jun;290(6):F1320-8
references: 16396941
references: J Membr Biol. 2001 Nov 1;184(1):71-9
references: 11687880
references: Cell Tissue Res. 1977 Nov 30;185(1):105-13
references: 589661
references: FEBS Lett. 2007 May 1;581(9):1783-7
references: 17428477
references: Stem Cells. 2012 Nov;30(11):2561-70
references: 22969057
references: Curr Biol. 2013 May 20;23(10):906-11
references: 23623554
references: Cell Motil Cytoskeleton. 1987;7(3):187-97
references: 2885096
references: J Am Soc Nephrol. 2009 Feb;20(2):278-88
references: 19158352
references: Circ Res. 2009 Apr 10;104(7):860-9
references: 19265036
references: J Cell Sci. 1985 Oct;78:283-310
references: 4093475
references: Nat Genet. 2003 Feb;33(2):129-37
references: 12514735
references: Cell Biol Int. 2004;28(2):101-10
references: 14984755
references: J Physiol (Paris). 1977;73(6):725-848
references: 340646
references: Curr Biol. 2002 Jun 4;12(11):R378-80
references: 12062067
references: Matrix Biol. 2007 May;26(4):234-46
references: 17289363
references: Biochim Biophys Acta. 2006 Jul;1759(7):348-58
references: 16934889
references: Am J Physiol Renal Physiol. 2005 Nov;289(5):F978-88
references: 15972389
references: Am J Physiol Renal Physiol. 2007 Mar;292(3):F930-45
references: 17090781
references: Cell Tissue Res. 1977 May 31;180(3):367-81
references: 872201
references: EMBO J. 1995 May 1;14(9):2043-55
references: 7538070
references: Science. 2012 Oct 12;338(6104):226-31
references: 22983710
references: Exp Cell Res. 1980 Apr;126(2):427-37
references: 6988225
references: Development. 2004 Jul;131(14):3457-67
references: 15226261
references: Nat Cell Biol. 2002 Mar;4(3):191-7
references: 11854751
references: J Cell Sci. 1985 Oct;78:311-36
references: 4093476
references: Exp Cell Res. 1979 Oct 15;123(2):444-9
references: 499374
references: Genet Med. 2009 Jun;11(6):386-402
references: 19421068
references: Development. 2010 Apr;137(7):1107-16
references: 20215348
references: Am J Physiol Renal Physiol. 2010 May;298(5):F1096-102
references: 20089672
references: Hum Mol Genet. 2007 Apr 15;16(8):942-56
references: 17470460
references: Mol Cell Biol. 1998 Aug;18(8):4855-62
references: 9671494
references: J Biol Chem. 1999 Oct 1;274(40):28557-65
references: 10497221
references: J Ultrastruct Res. 1984 Jun;87(3):212-20
references: 6085808
references: J Biol Chem. 2004 Aug 13;279(33):35009-16
references: 15194699
references: Curr Biol. 2014 Mar 3;24(5):519-25
references: 24530063
references: Nature. 2002 Sep 19;419(6904):312-6
references: 12239571
references: Cell. 2003 Jul 11;114(1):61-73
references: 12859898
references: Cell Mol Life Sci. 2014 Jun;71(11):2165-78
references: 24104765
references: J Am Soc Nephrol. 2002 Oct;13(10):2508-16
references: 12239239
references: J Cell Biol. 1972 May;53(2):494-509
references: 4554367
references: Gastroenterology. 2006 Dec;131(6):1856-69
references: 17123526
references: Cell Tissue Res. 1981;220(4):685-97
references: 7296649
references: Gastroenterology. 2006 Sep;131(3):911-20
references: 16952559
references: J Am Soc Nephrol. 2006 Apr;17(4):1015-25
references: 16565258