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《第二届全国发育生物学大会论文集》2014年
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Requirement of Smurf-Mediated Endocytosis of Patched1 in Sonic Hedgehog Signal Reception

Shen Yue  Liu-ya Tang  Ying Tang  Yi Tang  Qiu-hong Shen  Jie Ding  Yan Chen  Zengdi Zhang  Ting-ting Yu  Ying E.Zhang  Steven Y.Cheng  
【摘要】:正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 Patched 1(Ptch1),comprising two"PPXY"motifs,that direct it to degradation in lysosomes.These signals are recognized by two HECT-domain ubiquitin E3 ligases,Smurfl and Smurf2,which are induced by Shh and become enriched in Caveolin-1 lipid rafts in association with Rchl.Smurf-mediated endocytic turnover of Ptchl 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 Ptchl negative feedback loop that precisely controls the signaling output in response to Shh gradient signal.

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