Requirement of Smurf-mediated endocytosis of Patched1 in sonic hedgehog signal reception

  • Yue S
  • Tang L
  • Tang Y
 et al. 
  • 38

    Readers

    Mendeley users who have this article in their library.
  • 28

    Citations

    Citations of this article.

Abstract

Cell surface reception of Sonic hedgehog (Shh) must ensure that the graded morphogenic signal is interpreted accordingly in neighboring cells to specify tissue patterns during development. Here, we report endocytic sorting signals for the receptor Patched1 (Ptch1), comprising two 'PPXY' motifs, that direct it to degradation in lysosomes. These signals are recognized by two HECT-domain ubiquitin E3 ligases, Smurf1 and Smurf2, which are induced by Shh and become enriched in Caveolin-1 lipid rafts in association with Ptch1. Smurf-mediated endocytic turnover of Ptch1 is essential for its clearance from the primary cilium and pathway activation. Removal of both Smurfs completely abolishes the ability of Shh to sustain the proliferation of postnatal granule cell precursors in the cerebellum. These findings reveal a novel step in the Shh pathway activation as part of the Ptch1 negative feedback loop that precisely controls the signaling output in response to Shh gradient signal.

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Authors

  • Shen Yue

  • Liu Ya Tang

  • Ying Tang

  • Yi Tang

  • Qiu Hong Shen

  • Jie Ding

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free