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

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 h...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4653743/
https://www.ncbi.nlm.nih.gov/pubmed/26585507
http://dx.doi.org/10.1038/srep16506
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author 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
author_facet 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
author_sort Li, Wei
collection PubMed
description 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.
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spelling pubmed-46537432015-11-25 Sperm Associated Antigen 6 (SPAG6) Regulates Fibroblast Cell Growth, Morphology, Migration and Ciliogenesis 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 Sci Rep Article 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. Nature Publishing Group 2015-11-20 /pmc/articles/PMC4653743/ /pubmed/26585507 http://dx.doi.org/10.1038/srep16506 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
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
Sperm Associated Antigen 6 (SPAG6) Regulates Fibroblast Cell Growth, Morphology, Migration and Ciliogenesis
title Sperm Associated Antigen 6 (SPAG6) Regulates Fibroblast Cell Growth, Morphology, Migration and Ciliogenesis
title_full Sperm Associated Antigen 6 (SPAG6) Regulates Fibroblast Cell Growth, Morphology, Migration and Ciliogenesis
title_fullStr Sperm Associated Antigen 6 (SPAG6) Regulates Fibroblast Cell Growth, Morphology, Migration and Ciliogenesis
title_full_unstemmed Sperm Associated Antigen 6 (SPAG6) Regulates Fibroblast Cell Growth, Morphology, Migration and Ciliogenesis
title_short Sperm Associated Antigen 6 (SPAG6) Regulates Fibroblast Cell Growth, Morphology, Migration and Ciliogenesis
title_sort sperm associated antigen 6 (spag6) regulates fibroblast cell growth, morphology, migration and ciliogenesis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4653743/
https://www.ncbi.nlm.nih.gov/pubmed/26585507
http://dx.doi.org/10.1038/srep16506
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