Nuclear Export of Smads by RanBP3L Regulates Bone Morphogenetic Protein Signaling and Mesenchymal Stem Cell Differentiation. Academic Article uri icon

Overview

abstract

  • Bone morphogenetic proteins (BMPs) play vital roles in regulating stem cell maintenance and differentiation. BMPs can induce osteogenesis and inhibit myogenesis of mesenchymal stem cells. Canonical BMP signaling is stringently controlled through reversible phosphorylation and nucleocytoplasmic shuttling of Smad1, Smad5, and Smad8 (Smad1/5/8). However, how the nuclear export of Smad1/5/8 is regulated remains unclear. Here we report that the Ran-binding protein RanBP3L acts as a nuclear export factor for Smad1/5/8. RanBP3L directly recognizes dephosphorylated Smad1/5/8 and mediates their nuclear export in a Ran-dependent manner. Increased expression of RanBP3L blocks BMP-induced osteogenesis of mouse bone marrow-derived mesenchymal stem cells and promotes myogenic induction of C2C12 mouse myoblasts, whereas depletion of RanBP3L expression enhances BMP-dependent stem cell differentiation activity and transcriptional responses. In conclusion, our results demonstrate that RanBP3L, as a nuclear exporter for BMP-specific Smads, plays a critical role in terminating BMP signaling and regulating mesenchymal stem cell differentiation.

publication date

  • March 9, 2015

Research

keywords

  • Bone Morphogenetic Proteins
  • Cell Nucleus
  • Mesenchymal Stem Cells
  • Nuclear Proteins
  • Nucleocytoplasmic Transport Proteins
  • Smad Proteins

Identity

PubMed Central ID

  • PMC4405638

Scopus Document Identifier

  • 84929170080

Digital Object Identifier (DOI)

  • 10.1016/j.molcel.2007.12.024

PubMed ID

  • 25755279

Additional Document Info

volume

  • 35

issue

  • 10