TY - JOUR
T1 - Rabconnectin-3 is a functional regulator of mammalian notch signaling
AU - Sethi, Nilay
AU - Yan, Yan
AU - Quek, Debra
AU - Schupbach, Trudi
AU - Kang, Yibin
PY - 2010/11/5
Y1 - 2010/11/5
N2 - The Notch signaling pathway is important for cell fate decisions in embryonic development and adult life. Defining the functional importance of the Notch pathway in these contexts requires the elucidation of essential signal transduction components that have not been fully characterized. Here, we show that Rabconnectin-3B is required for the Notch pathway in mammalian cells. siRNA-mediated silencing of Rabconnectin-3B in mammalian cells attenuated Notch signaling and disrupted the activation and nuclear accumulation of the Notch target Hes1. Rabconnectin-3B knockdown also disrupted V-ATPase activity in mammalian cells, consistent with previous observations in Drosophila. Pharmacological inhibition of the V-ATPase complex significantly reduced Notch signaling in mammalian cells. Finally, Rabconnectin-3B knockdown phenocopied functional disruption of Notch signaling during osteoclast differentiation. Collectively, these findings define an important role for Rabconnectin-3 and V-ATPase activity in the Notch signaling pathway in mammalian cells.
AB - The Notch signaling pathway is important for cell fate decisions in embryonic development and adult life. Defining the functional importance of the Notch pathway in these contexts requires the elucidation of essential signal transduction components that have not been fully characterized. Here, we show that Rabconnectin-3B is required for the Notch pathway in mammalian cells. siRNA-mediated silencing of Rabconnectin-3B in mammalian cells attenuated Notch signaling and disrupted the activation and nuclear accumulation of the Notch target Hes1. Rabconnectin-3B knockdown also disrupted V-ATPase activity in mammalian cells, consistent with previous observations in Drosophila. Pharmacological inhibition of the V-ATPase complex significantly reduced Notch signaling in mammalian cells. Finally, Rabconnectin-3B knockdown phenocopied functional disruption of Notch signaling during osteoclast differentiation. Collectively, these findings define an important role for Rabconnectin-3 and V-ATPase activity in the Notch signaling pathway in mammalian cells.
UR - http://www.scopus.com/inward/record.url?scp=78049397293&partnerID=8YFLogxK
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U2 - 10.1074/jbc.M110.158634
DO - 10.1074/jbc.M110.158634
M3 - Article
C2 - 20810660
AN - SCOPUS:78049397293
SN - 0021-9258
VL - 285
SP - 34757
EP - 34764
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 45
ER -