The Angiotensin II Type 1 Receptor C-Terminal Lys Residues Interact with Tubulin and Modulate Receptor Export Trafficking
Open Access
- 25 February 2013
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 8 (2), e57805
- https://doi.org/10.1371/journal.pone.0057805
Abstract
The physiological and pathological functions of angiotensin II are largely mediated through activating the cell surface angiotensin II type 1 receptor (AT1R). However, the molecular mechanisms underlying the transport of newly synthesized AT1R from the endoplasmic reticulum (ER) to the cell surface remain poorly defined. Here we demonstrated that the C-terminus (CT) of AT1R directly and strongly bound to tubulin and the binding domains were mapped to two consecutive Lys residues at positions 310 and 311 in the CT membrane-proximal region of AT1R and the acidic CT of tubulin, suggestive of essentially ionic interactions between AT1R and tubulin. Furthermore, mutation to disrupt tubulin binding dramatically inhibited the cell surface expression of AT1R, arrested AT1R in the ER, and attenuated AT1R-mediated signaling measured as ERK1/2 activation. These data demonstrate for the first time that specific Lys residues in the CT juxtamembrane region regulate the processing of AT1R through interacting with tubulin. These data also suggest an important role of the microtubule network in the cell surface transport of AT1R.This publication has 52 references indexed in Scilit:
- Small GTPase regulation of GPCR anterograde traffickingTrends in Pharmacological Sciences, 2012
- Di-acidic Motifs in the Membrane-distal C Termini Modulate the Transport of Angiotensin II Receptors from the Endoplasmic Reticulum to the Cell SurfaceOnline Journal of Public Health Informatics, 2011
- Rab1 GTPase regulates phenotypic modulation of pulmonary artery smooth muscle cells by mediating the transport of angiotensin II type 1 receptor under hypoxiaThe International Journal of Biochemistry & Cell Biology, 2011
- Rab8 Interacts with Distinct Motifs in α2B- and β2-Adrenergic Receptors and Differentially Modulates Their TransportOnline Journal of Public Health Informatics, 2010
- Aberrant trafficking of human melanocortin 1 receptor variants associated with red hair and skin cancer: Steady‐state retention of mutant forms in the proximal golgiJournal of Cellular Physiology, 2009
- Tubulin binding blocks mitochondrial voltage-dependent anion channel and regulates respirationProceedings of the National Academy of Sciences of the United States of America, 2008
- Endoplasmic reticulum export of adrenergic and angiotensin II receptors is differentially regulated by Sar1 GTPaseCellular Signalling, 2008
- Regulation of anterograde transport of adrenergic and angiotensin II receptors by Rab2 and Rab6 GTPasesCellular Signalling, 2007
- Structural Basis of Microtubule Plus End Tracking by XMAP215, CLIP-170, and EB1Molecular Cell, 2007
- Structural basis for tubulin recognition by cytoplasmic linker protein 170 and its autoinhibitionProceedings of the National Academy of Sciences of the United States of America, 2007