title: The angiotensin II type 1 receptor C-terminal Lys residues interact with tubulin and modulate receptor export trafficking.
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.
authors: Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, Louisiana, United States of America.
authors: Xiaoping
authors: X
authors: Zhang
authors: Hong
authors: H
authors: Wang
authors: Matthew T
authors: MT
authors: Duvernay
authors: Shu
authors: S
authors: Zhu
authors: Guangyu
authors: G
authors: Wu
mesh_terms: D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D008239:Lysine / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D009154:Mutation; D021381:Protein Transport; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014404:Tubulin / Q000235:genetics / Q000378:metabolism*
chemical_list: D044140:Receptor, Angiotensin, Type 1; D014404:Tubulin; D008239:Lysine