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

• Published in: Scientific reports 2015-11, Vol.5 (1), p.16506-16506, Article 16506
• Main Authors: Li, Wei, Mukherjee, Abir, Wu, Jinhua, Zhang, Ling, Teves, Maria E., Li, Hongfei, Nambiar, Shanti, Henderson, Scott C., Horwitz, Alan R., Strauss III, Jerome F., Fang, Xianjun, Zhang, Zhibing
• Format: Article
• Language: English
• Subjects: 13/51; 14/1; 14/19; 14/28; 14/63; 631/337/458/1275; 631/80/128; Actin; Animals; Blotting, Western; Cell Adhesion - genetics; Cell morphology; Cell Movement - genetics; Cell Proliferation - genetics; Cell Survival - genetics; Centrosomes; Cercopithecus aethiops; CHO Cells; Cilia; Cilia - genetics; Cilia - metabolism; COS Cells; Cricetinae; Cricetulus; Cytology; Cytoskeleton - metabolism; Embryo fibroblasts; Embryo, Mammalian - cytology; Fibroblasts - drug effects; Fibroblasts - metabolism; Fibroblasts - ultrastructure; Flagella; Humanities and Social Sciences; Mice, Knockout; Microscopy, Confocal; Microscopy, Electron, Scanning; Microtubule Proteins - genetics; Microtubule Proteins - metabolism; Microtubules; Morphology; Motility; multidisciplinary; Paclitaxel; Paclitaxel - pharmacology; Science; Surface area; Tubulin; Tubulin - metabolism; Tubulin Modulators - pharmacology; Wound healing
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep16506

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 immortalized Spag6 -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 the Spag6 -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.