A Novel Signaling Pathway Mediated by the Nuclear Targeting of C-terminal Fragments of Mammalian Patched 1

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2011 May 3

PMID 21533246

Citations 10

Authors

Hiroki Kagawa

Yuka Shino

Daigo Kobayashi

Syunsuke Demizu

Masumi Shimada

Hiroyoshi Ariga

Hiroyuki Kawahara

Affiliations

Soon will be listed here.

Abstract

Background: Patched 1 (Ptc1) is a polytopic receptor protein that is essential for growth and differentiation. Its extracellular domains accept its ligand, Sonic Hedgehog, while the function of its C-terminal intracellular domain is largely obscure.

Principal Findings: In this study, we stably expressed human Ptc1 protein in HeLa cells and found that it is subjected to proteolytic cleavage at the C-terminus, resulting in the generation of soluble C-terminal fragments. These fragments accumulated in the nucleus, while the N-terminal region of Ptc1 remained in the cytoplasmic membrane fractions. Using an anti-Ptc1 C-terminal domain antibody, we provide conclusive evidence that C-terminal fragments of endogenous Ptc1 accumulate in the nucleus of C3H10T1/2 cells. Similar nuclear accumulation of endogenous C-terminal fragments was observed not only in C3H10T1/2 cells but also in mouse embryonic primary cells. Importantly, the C-terminal fragments of Ptc1 modulate transcriptional activity of Gli1.

Conclusions: Although Ptc1 protein was originally thought to be restricted to cell membrane fractions, our findings suggest that its C-terminal fragments can function as an alternative signal transducer that is directly transported to the cell nucleus.

Citing Articles

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Hedgehog signaling and its molecular perspective with cholesterol: a comprehensive review.

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Loss of the homologous recombination gene leads to Fanconi anemia-like symptoms in zebrafish.

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The C-terminal cytoplasmic tail of hedgehog receptor Patched1 is a platform for E3 ubiquitin ligase complexes.

Yamaki Y, Kagawa H, Hatta T, Natsume T, Kawahara H Mol Cell Biochem. 2016; 414(1-2):1-12.

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