TY - JOUR
T1 - TGF-β Signaling Is Associated with Endocytosis at the Pocket Region of the Primary Cilium
AU - Clement, Christian Alexandro
AU - Ajbro, Katrine Dalsgaard
AU - Koefoed, Karen
AU - Vestergaard, Maj Linea
AU - Veland, Iben Rønn
AU - Perestrello Ramos H de Jesus, Maria
AU - Pedersen, Lotte Bang
AU - Benmerah, Alexandre
AU - Andersen, Claus Yding
AU - Larsen, Lars Allan
AU - Christensen, Søren Tvorup
N1 - Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.
PY - 2013/3/27
Y1 - 2013/3/27
N2 - Transforming growth factor β (TGF-β) signaling is regulated by clathrin-dependent endocytosis (CDE) for the control of cellular processes during development and in tissue homeostasis. The primary cilium coordinates several signaling pathways, and the pocket surrounding the base and proximal part of the cilium is a site for CDE. We report here that TGF-β receptors localize to the ciliary tip and endocytic vesicles at the ciliary base in fibroblasts and that TGF-β stimulation increases receptor localization and activation of SMAD2/3 and ERK1/2 at the ciliary base. Inhibition of CDE reduced TGF-β-mediated signaling at the cilium, and TGF-β signaling and CDE activity are reduced at stunted primary cilia in Tg737orpk fibroblasts. Similarly, TGF-β signaling during cardiomyogenesis correlated with accumulation of TGF-β receptors and activation of SMAD2/3 at the ciliary base. Our results indicate that the primary cilium regulates TGF-β signaling and that the ciliary pocket is a compartment for CDE-dependent regulation of signal transduction.
AB - Transforming growth factor β (TGF-β) signaling is regulated by clathrin-dependent endocytosis (CDE) for the control of cellular processes during development and in tissue homeostasis. The primary cilium coordinates several signaling pathways, and the pocket surrounding the base and proximal part of the cilium is a site for CDE. We report here that TGF-β receptors localize to the ciliary tip and endocytic vesicles at the ciliary base in fibroblasts and that TGF-β stimulation increases receptor localization and activation of SMAD2/3 and ERK1/2 at the ciliary base. Inhibition of CDE reduced TGF-β-mediated signaling at the cilium, and TGF-β signaling and CDE activity are reduced at stunted primary cilia in Tg737orpk fibroblasts. Similarly, TGF-β signaling during cardiomyogenesis correlated with accumulation of TGF-β receptors and activation of SMAD2/3 at the ciliary base. Our results indicate that the primary cilium regulates TGF-β signaling and that the ciliary pocket is a compartment for CDE-dependent regulation of signal transduction.
U2 - 10.1016/j.celrep.2013.05.020
DO - 10.1016/j.celrep.2013.05.020
M3 - Journal article
C2 - 23746451
SN - 2211-1247
VL - 3
SP - 1806
EP - 1814
JO - Cell Reports
JF - Cell Reports
IS - 6
ER -