title: Sperm-associated antigen 6 (SPAG6) deficiency and defects in ciliogenesis and cilia function: polarity, density, and beat.
abstract: SPAG6, an axoneme central apparatus protein, is essential for function of ependymal cell cilia and sperm flagella. A significant number of Spag6-deficient mice die with hydrocephalus, and surviving males are sterile because of sperm motility defects. In further exploring the ciliary dysfunction in Spag6-null mice, we discovered that cilia beat frequency was significantly reduced in tracheal epithelial cells, and that the beat was not synchronized. There was also a significant reduction in cilia density in both brain ependymal and trachea epithelial cells, and cilia arrays were disorganized. The orientation of basal feet, which determines the direction of axoneme orientation, was apparently random in Spag6-deficient mice, and there were reduced numbers of basal feet, consistent with reduced cilia density. The polarized epithelial cell morphology and distribution of intracellular mucin, α-tubulin, and the planar cell polarity protein, Vangl2, were lost in Spag6-deficient tracheal epithelial cells. Polarized epithelial cell morphology and polarized distribution of α-tubulin in tracheal epithelial cells was observed in one-week old wild-type mice, but not in the Spag6-deficient mice of the same age. Thus, the cilia and polarity defects appear prior to 7 days post-partum. These findings suggest that SPAG6 not only regulates cilia/flagellar motility, but that in its absence, ciliogenesis, axoneme orientation, and tracheal epithelial cell polarity are altered.
authors.affiliation: Department of Obstetrics and Gynecology, Virginia Commonwealth University, Richmond, Virginia, United States of America.
authors.forename: Maria E
authors.initials: ME
authors.lastname: Teves
authors.affiliation: Cystic Fibrosis Center, University of North Carolina, Chapel Hill, North Carolina, United States of America.
authors.forename: Patrick R
authors.initials: PR
authors.lastname: Sears
authors.affiliation: Department of Obstetrics and Gynecology, Virginia Commonwealth University, Richmond, Virginia, United States of America.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Obstetrics and Gynecology, Virginia Commonwealth University, Richmond, Virginia, United States of America; Department of Infectious Diseases, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Zhengang
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Otorhinolaryngology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Waixing
authors.initials: W
authors.lastname: Tang
authors.affiliation: Department of Obstetrics and Gynecology, Virginia Commonwealth University, Richmond, Virginia, United States of America.
authors.forename: Lauren
authors.initials: L
authors.lastname: van Reesema
authors.affiliation: Department of Physiology and Biophysics, Virginia Commonwealth University, Richmond, Virginia, United States of America.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Costanzo
authors.affiliation: Department of Cell & Molecular Physiology of Medicine, University of North Carolina, Chapel Hill, North Carolina, United States of America.
authors.forename: C William
authors.initials: CW
authors.lastname: Davis
authors.affiliation: Department of Cell & Molecular Physiology of Medicine, University of North Carolina, Chapel Hill, North Carolina, United States of America.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Knowles
authors.affiliation: Department of Obstetrics and Gynecology, Virginia Commonwealth University, Richmond, Virginia, United States of America; Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, Virginia, United States of America.
authors.forename: Jerome F
authors.initials: JF
authors.lastname: Strauss
authors.affiliation: Department of Obstetrics and Gynecology, Virginia Commonwealth University, Richmond, Virginia, United States of America; Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, Virginia, United States of America.
authors.forename: Zhibing
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000818:Animals; D054468:Axoneme / Q000378:metabolism; D001921:Brain / Q000473:pathology; D016764:Cell Polarity; D002923:Cilia / Q000502:physiology*; D004805:Ependyma / Q000378:metabolism / Q000473:pathology; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008855:Microscopy, Electron, Scanning; D018715:Microscopy, Video; D008868:Microtubule Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014132:Trachea / Q000473:pathology
chemical_list: D008868:Microtubule Proteins; C504274:SPAG6 protein, mouse