Neurotensin-induced miR-133α expression regulates neurotensin receptor 1 recycling through its downstream target aftiphilin

Scientific Reports
Ivy Ka Man LawCharalabos Pothoulakis

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...Continue Reading

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Citations

Aug 5, 2017·American Journal of Physiology. Gastrointestinal and Liver Physiology·Ivy Ka Man LawCharalabos Pothoulakis
Jul 27, 2021·Frontiers in Pharmacology·Jing ZhouSimin Chen
Jan 22, 2022·Clinical and Translational Medicine·Ravinder Reddy GaddamAjit Vikram

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Methods Mentioned

BETA
immunoprecipitation
ELISA
confocal microscopy
PCR
ChIP
transfection

Software Mentioned

Zeiss
Image [UNK]
Transcription Element Search System ( TESS )
Zen

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