Projects per year
Abstract
Neurotensin (NT) triggers signaling in human colonic epithelial cells by activating the G protein-coupled receptor, the neurotensin receptor 1 (NTR1). Activated NTR1 traffics from the plasma membrane to early endosomes, and then recycles. Although sustained NT/NTR1 signaling requires efficient NTR1 recycling, little is known about the regulation of NTR1 recycling. We recently showed that NT/NTR1 signaling increases expression of miR-133α. Herein, we studied the mechanism of NT-regulated miR-133α expression and examined the role of miR-133α in intracellular NTR1 trafficking in human NCM460 colonocytes. We found that NT-induced miR-133α upregulation involves the negative transcription regulator, zinc finger E-box binding homeobox 1. Silencing of miR-133α or overexpression of aftiphilin (AFTPH), a binding target of miR-133α, attenuated NTR1 trafficking to plasma membrane in human colonocytes, without affecting NTR1 internalization. We localized AFTPH to early endosomes and the trans-Golgi network (TGN) in unstimulated human colonic epithelial cells. AFTPH overexpression reduced NTR1 localization in early endosomes and increased expression of proteins related to endosomes and the TGN trafficking pathway. AFTPH overexpression and de-acidification of intracellular vesicles increased NTR1 expression. Our results suggest a novel mechanism of GPCR trafficking in human colonic epithelial cells by which a microRNA, miR-133α regulates NTR1 trafficking through its downstream target AFTPH.
Original language | English |
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Article number | 22195 |
Number of pages | 14 |
Journal | Scientific Reports |
Volume | 6 |
DOIs | |
Publication status | Published - 23 Feb 2016 |
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Mechanisms of protease-driven visceral pain
Graham, B. (Primary Chief Investigator (PCI)), Brierley, S. (Chief Investigator (CI)), Poole, D. (Chief Investigator (CI)) & Bunnett, N. (Associate Investigator (AI))
National Health and Medical Research Council (NHMRC) (Australia)
1/01/13 → 31/12/15
Project: Research
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Bile Acid and Neurosteroid Signaling to the Nervous System
Bunnett, N. (Primary Chief Investigator (PCI)), McIntyre, P. (Chief Investigator (CI)) & Poole, D. (Partner Investigator (PI))
National Health and Medical Research Council (NHMRC) (Australia)
1/01/12 → 31/12/14
Project: Research
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Australian Fellowship Round 4 (2011 - 2015): Building a new research program into the mechanism, diagnosis and treatment of chronic inflammatory disease.
Bunnett, N. (Primary Chief Investigator (PCI))
National Health and Medical Research Council (NHMRC) (Australia)
1/06/11 → 31/08/16
Project: Research