Palmitoylation of human thyrotropin receptor: slower intracellular trafficking of the palmitoylation-defective mutant

Endocrinology
K TanakaM Niwa

Abstract

We here show that the epitope-tagged human TSH receptor (TSHRmyc) is covalently modified with palmitic acid by thioesterification. Side-directed mutagenesis identified Cys699 in the C-terminal cytoplasmic tail of the receptor as the putative palmitoylation site. Mutation of Cys699 to Ala results in the nonpalmitoylated receptor (TSHRmycC699A) in which high affinity TSH binding, Gs coupling, homologous desensitization and TSH-induced internalization are unaffected. In contrast, abolition of palmitoylation appears to decrease the rate of the intracellular trafficking of the receptor. However, since most of TSHRmycC699A seems to be fully processed finally and the receptor number of TSHRmycC699A on the cell surface is comparable to that of TSHRmyc, our results suggest that abolition of palmitoylation delays the cell surface expression of TSHR, but does not trap the receptor intracellularly, although another possibility for proteolytic degradation of either the 95 kDa or the 100 kDa mutant receptor can not be excluded. Thus, post-translational modification of TSHR by palmitoylation may provide a novel mechanism of enhancing the rate of intracellular trafficking of the receptor.

Citations

Apr 27, 2005·The Journal of Biological Chemistry·Zhongyan WangJanis Lem
Feb 5, 2008·Endocrine·Alfredo Ulloa-AguirreJames A Dias
Nov 21, 2007·Endocrine Journal·Eijun NishiharaAkira Miyauchi
Dec 21, 2002·Pharmacology & Therapeutics·Riad Qanbar, Michel Bouvier
Jun 6, 2003·British Journal of Pharmacology·Nicholas D Holliday, Helen M Cox
Jun 29, 2013·Molecular and Cellular Endocrinology·Alfredo Ulloa-AguirreP Michael Conn
Mar 15, 2015·Expert Opinion on Therapeutic Targets·Terry F Davies, Rauf Latif
Oct 19, 2006·Molecular and Cellular Endocrinology·Alfredo Ulloa-AguirreJames A Dias
Oct 28, 2006·Biochimica Et Biophysica Acta·Pablo V EscribáOliver Vögler
Jan 7, 1999·FEBS Letters·C ChenL Y Liu-Chen
Aug 22, 2013·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Junxian LimDavid P Fairlie
Aug 1, 2006·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Francois RouzaudVincent J Hearing
Oct 31, 2008·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·P GonnordJ M Kanellopoulos
Apr 6, 2006·The Journal of Biological Chemistry·Ulla E Petäjä-RepoMichel Bouvier
Jun 8, 2001·The Journal of Biological Chemistry·Y PercherancierF Bachelerie
Mar 17, 2005·Journal of Cell Science·Christina M Van ItallieJames M Anderson
Oct 3, 2002·Science's STKE : Signal Transduction Knowledge Environment·Luc G Berthiaume

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.