Sperm Associated Antigen 6 (SPAG6) Regulates Fibroblast Cell Growth, Morphology, Migration and Ciliogenesis

Authors

Wei Li, Virginia Commonwealth UniversityFollow
Abir Mukherjee, Virginia Commonwealth University
Jinhua Wu, Virginia Commonwealth University
Ling Zhang, Virginia Commonwealth University
Maria E. Teves, Virginia Commonwealth UniversityFollow
Hongfei Li, Virginia Commonwealth UniversityFollow
Shanti Nambiar, Virginia Commonwealth UniversityFollow
Scott C. Henderson, Virginia Commonwealth UniversityFollow
Alan R. Horwitz, University of Virginia
Jerome F. Strauss III, Virginia Commonwealth University School of MedicineFollow
Xianjun Fang, Virginia Commonwealth UniversityFollow
Zhibing Zhang, Virginia Commonwealth UniversityFollow

Document Type

Article

Original Publication Date

2015

Journal/Book/Conference Title

Scientific Reports

Volume

5

Issue

Article number: 16506

DOI of Original Publication

10.1038/srep16506

Comments

Originally published at http://dx.doi.org/10.1038/srep16506

Date of Submission

April 2016

Abstract

Mammalian Spag6 is the orthologue of Chlamydomonas PF16, which encodes a protein localized in the axoneme central apparatus, and regulates flagella/cilia motility. Most Spag6-deficient mice are smaller in size than their littermates. Because SPAG6 decorates microtubules, we hypothesized that SPAG6 has other roles related to microtubule function besides regulating flagellar/cilia motility. Mouse embryonic fibroblasts (MEFs) were isolated from Spag6-deficient and wild-type embryos for these studies. Both primary and immortalizedSpag6-deficient MEFs proliferated at a much slower rate than the wild-type MEFs, and they had a larger surface area. Re-expression of SPAG6 in the Spag6-deficient MEFs rescued the abnormal cell morphology. Spag6-deficient MEFs were less motile than wild-type MEFs, as shown by both chemotactic analysis and wound-healing assays. Spag6-deficient MEFs also showed reduced adhesion associated with a non-polarized F-actin distribution. Multiple centrosomes were observed in theSpag6-deficient MEF cultures. The percentage of cells with primary cilia was significantly reduced compared to the wild-type MEFs, and some Spag6-deficient MEFs developed multiple cilia. Furthermore, SPAG6 selectively increased expression of acetylated tubulin, a microtubule stability marker. The Spag6-deficient MEFs were more sensitive to paclitaxel, a microtubule stabilizer. Our studies reveal new roles for SPAG6 in modulation of cell morphology, proliferation, migration, and ciliogenesis.

Rights

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Is Part Of

VCU Obstetrics and Gynecology Publications