Zfyve16 regulates the proliferation of B-lymphoid cells

Abstract

Zfyve16 (a.k.a. endofin or endosome-associated FYVE-domain protein), a member of the FYVE-domain protein family, is involved in endosomal trafficking and in TGF-β, BMP, and EGFR signaling. The FYVE protein SARA regulates the TGF-β signaling pathway by recruiting Smad2/3 and accelerating their phosphorylation, thereby altering their susceptibility to TGF-β-mediated T cell suppression. Zfyve16 binds to Smad4 and their binding affects the formation of Smad2/3-Smad4 complex in TGF-β signaling. However, the in vivo function of Zfyve16 remains unknown. In this study, we generated a Zfyve16 knockout mouse strain (Zfyve16^KO) and examined its hematopoietic phenotypes and hematopoietic reconstruction ability. The proportion of T cells in the peripheral blood of Zfyve16^KO mice increases compared with that in wild-type mice. This finding is consistent with the role of Zfyve16 in facilitating TGF-β signaling. Unpredictably, B cell proliferation is inhibited in Zfyve16^KO mice. The proliferation potential of Zfyve16^KO B-lymphoid cells also significantly decreases in vitro. These results suggest that Zfyve16 inhibits the proliferation of T cells, possibly through the TGF-β signaling, but upregulates the proliferation of B-lymphoid cells.

Keywords

Zfyve16 / endofin / hematopoiesis / TGF-β / lymphocytes

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Acknowledgements

This work was supported by the National Key Research and Development Program of China (No. 2016YFC0902800), National Natural Science Foundation of China (Nos. 81230055 and 81530006 to Ruibao Ren), and the Samuel Waxman Cancer Research Foudation Co-PI Program. We thank Huanbin Zhao, Min Wu, Chun Zhang, Mingzhu Liu, Zhangsen Huang, and Lingyun Tang for technical assistance.

Compliance with ethics guidelines

Xuemei Zhao, Donghe Li, Qingsong Qiu, Bo Jiao, Ruihong Zhang, Ping Liu, and Ruibao Ren declare that they have no conflict of interest. All institutional and national guidelines for the care and use of laboratory animals were followed.

Electronic Supplementary Material

Supplementary material is available in the online version of this article at http://doi.org/10.1007/s11684-017-0562-3 and is accessible for authorized users.

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