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Nuclear Fibroblast Growth Factor Receptor Signaling in Skeletal Development and Disease

  • Skeletal Development (R Marcucio and J Feng, Section Editors)
  • Published:
Current Osteoporosis Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Fibroblast growth factor receptor (FGFR) signaling regulates proliferation and differentiation during development and homeostasis. While membrane-bound FGFRs play a central role in these processes, the function of nuclear FGFRs is also critical. Here, we highlight mechanisms for nuclear FGFR translocation and the effects of nuclear FGFRs on skeletal development and disease.

Recent Findings

Full-length FGFRs, internalized by endocytosis, enter the nucleus through β-importin-dependent mechanisms that recognize the nuclear localization signal within FGFs. Alternatively, soluble FGFR intracellular fragments undergo nuclear translocation following their proteolytic release from the membrane. FGFRs enter the nucleus during the cellular transition between proliferation and differentiation. Once nuclear, FGFRs interact with chromatin remodelers to alter the epigenetic state and transcription of their target genes. Dysregulation of nuclear FGFR is linked to the etiology of congenital skeletal disorders and neoplastic transformation.

Summary

Revealing the activities of nuclear FGFR will advance our understanding of 20 congenital skeletal disorders caused by FGFR mutations, as well as FGFR-related cancers.

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Acknowledgments

The authors thank all the members of the Merrill laboratory for insightful discussions and, in particular, Lauren Bobzin for her critical review of this manuscript.

Funding

This work was supported by the National Institutes of Health R01DE025222 to A.E.M.

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Authors and Affiliations

  1. Center for Craniofacial Molecular Biology, Herman Ostrow School of Dentistry, University of Southern California, Los Angeles, CA, 90033, USA

    Creighton T. Tuzon, Diana Rigueur & Amy E. Merrill

  2. Department of Biochemistry and Molecular Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA

    Amy E. Merrill

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  1. Creighton T. Tuzon
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Correspondence to Amy E. Merrill.

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Tuzon, C.T., Rigueur, D. & Merrill, A.E. Nuclear Fibroblast Growth Factor Receptor Signaling in Skeletal Development and Disease. Curr Osteoporos Rep 17, 138–146 (2019). https://doi.org/10.1007/s11914-019-00512-2

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