TY - JOUR
T1 - BBS4 regulates the expression and secretion of FSTL1, a protein that participates in ciliogenesis and the differentiation of 3T3-L1
AU - Prieto-Echagüe, Victoria
AU - Lodh, Sukanya
AU - Colman, Laura
AU - Bobba, Natalia
AU - Santos, Leonardo
AU - Katsanis, Nicholas
AU - Escande, Carlos
AU - Zaghloul, Norann A.
AU - Badano, Jose L.
N1 - Funding Information:
We thank Magdalena Cárdenas-Rodríguez, Florencia Irigoín, Paola Lepanto, Rossina Novas, Belén Torrado and Matías Fabregat for discussions and help along different stages of this work and Maine Fariello for her help with statistical analysis. We also thank other members of the INDICyO Program and in particular Dr. Carlos Batthyány and Dr. Marcelo Hill for sharing reagents and helpful discussions. This study was supported by MERCOSUR Structural Convergence Fund (FOCEM, COF 03/11). VP, NB, LS, CE, and JLB are supported by the “Programa de Desarrollo de las Ciencias Básicas”, PEDECIBA, and by the Agencia Nacional de Investigación e Innovación (ANII), Uruguay. NZ is supported by NIH grant RO1DK102001 and the Mid-Atlantic Nutrition and Obesity Research Center (P30DK072488), and NK by NIH grant HD042601.
Publisher Copyright:
© 2017 The Author(s).
PY - 2017/12/1
Y1 - 2017/12/1
N2 - Bardet-Biedl syndrome is a model ciliopathy. Although the characterization of BBS proteins has evidenced their involvement in cilia, extraciliary functions for some of these proteins are also being recognized. Importantly, understanding both cilia and cilia-independent functions of the BBS proteins is key to fully dissect the cellular basis of the syndrome. Here we characterize a functional interaction between BBS4 and the secreted protein FSTL1, a protein linked to adipogenesis and inflammation among other functions. We show that BBS4 and cilia regulate FSTL1 mRNA levels, but BBS4 also modulates FSTL1 secretion. Moreover, we show that FSTL1 is a novel regulator of ciliogenesis thus underscoring a regulatory loop between FSTL1 and cilia. Finally, our data indicate that BBS4, cilia and FSTL1 are coordinated during the differentiation of 3T3-L1 cells and that FSTL1 plays a role in this process, at least in part, by modulating ciliogenesis. Therefore, our findings are relevant to fully understand the development of BBS-associated phenotypes such as obesity.
AB - Bardet-Biedl syndrome is a model ciliopathy. Although the characterization of BBS proteins has evidenced their involvement in cilia, extraciliary functions for some of these proteins are also being recognized. Importantly, understanding both cilia and cilia-independent functions of the BBS proteins is key to fully dissect the cellular basis of the syndrome. Here we characterize a functional interaction between BBS4 and the secreted protein FSTL1, a protein linked to adipogenesis and inflammation among other functions. We show that BBS4 and cilia regulate FSTL1 mRNA levels, but BBS4 also modulates FSTL1 secretion. Moreover, we show that FSTL1 is a novel regulator of ciliogenesis thus underscoring a regulatory loop between FSTL1 and cilia. Finally, our data indicate that BBS4, cilia and FSTL1 are coordinated during the differentiation of 3T3-L1 cells and that FSTL1 plays a role in this process, at least in part, by modulating ciliogenesis. Therefore, our findings are relevant to fully understand the development of BBS-associated phenotypes such as obesity.
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U2 - 10.1038/s41598-017-10330-0
DO - 10.1038/s41598-017-10330-0
M3 - Article
C2 - 28852127
AN - SCOPUS:85028464314
VL - 7
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 9765
ER -
