Sperm-Associated Antigen 6 (SPAG6) Deficiency and Defects in Ciliogenesis and Cilia Function: Polarity, Density, and Beat

Authors

Maria E. Teves, Virginia Commonwealth University
Patrick R. Sears, University of North Carolina
Wei Li, Virginia Commonwealth University
Zhengang Zhang, Virginia Commonwealth University, Huazhong University of Science and Technology
Waixing Tang, University of Pennsylvania
Lauren van Reesema, Virginia Commonwealth University
Richard M. Costanzo, Virginia Commonwealth University
C. William Davis, University of North Carolina
Michael R. Knowles, University of North Carolina
Jerome F. Strauss III, Virginia Commonwealth University
Zhibing Zhang, Virginia Commonwealth UniversityFollow

Document Type

Article

Original Publication Date

2014

Journal/Book/Conference Title

PLOS ONE

Volume

9

Issue

10

DOI of Original Publication

10.1371/journal.pone.0107271

Comments

Originally published at http://doi.org/10.1371/journal.pone.0107271.

Date of Submission

December 2016

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.

Rights

Copyright © 2014 Teves et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Is Part Of

VCU Obstetrics and Gynecology Publications