Structural and functional impairment of endocytic pathways by retinitis pigmentosa mutant rhodopsin-arrestin complexes

The Journal of Clinical Investigation
Jen-Zen ChuangChing-Hwa Sung

Abstract

Retinitis pigmentosa (RP) is a clinically and genetically heterogeneous degenerative eye disease. Mutations at Arg135 of rhodopsin are associated with a severe form of autosomal dominant RP. This report presents evidence that Arg135 mutant rhodopsins (e.g., R135L, R135G, and R135W) are hyperphosphorylated and bind with high affinity to visual arrestin. Mutant rhodopsin recruits the cytosolic arrestin to the plasma membrane, and the rhodopsin-arrestin complex is internalized into the endocytic pathway. Furthermore, the rhodopsin-arrestin complexes alter the morphology of endosomal compartments and severely damage receptor-mediated endocytic functions. The biochemical and cellular defects of Arg135 mutant rhodopsins are distinct from those previously described for class I and class II RP mutations, and, hence, we propose that they be named class III. Impaired endocytic activity may underlie the pathogenesis of RP caused by class III rhodopsin mutations.

References

Jan 1, 1992·DNA and Cell Biology·W C ProbstS C Sealfon
Oct 1, 1992·Neuron·P R RobinsonD D Oprian
Aug 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·C H SungJ Nathans
Oct 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·C H SungJ Nathans
Jun 20, 1991·Nature·G M RattoP A McNaughton
Oct 5, 1990·Science·R R FrankeK P Hofmann
Nov 20, 1989·Neuroscience Letters·J R Cotter
Jul 28, 1995·The Journal of Biological Chemistry·C K ChenJ B Hurley
Apr 11, 1995·Proceedings of the National Academy of Sciences of the United States of America·T LiT P Dryja
Aug 1, 1993·Journal of Cellular Physiology·A A Davis, R C Hunt
Jun 24, 1997·Proceedings of the National Academy of Sciences of the United States of America·J G FlanneryW W Hauswirth
Jan 3, 2001·Proceedings of the National Academy of Sciences of the United States of America·L S BarakM G Caron
Oct 5, 2001·Nature Reviews. Molecular Cell Biology·J Gruenberg
Jan 5, 2002·Proceedings of the National Academy of Sciences of the United States of America·Dror SharonThaddeus P Dryja
Sep 10, 2002·Nature Genetics·Wenshan HaoJanis Lem
Nov 15, 2002·Journal of Cell Science·Yang HuChing-Hwa Sung
Jan 17, 2003·Molecular Biology of the Cell·Satoshi WaguriBernard Hoflack
Nov 7, 2003·Proceedings of the National Academy of Sciences of the United States of America·Takahiko Matsuda, Constance L Cepko

❮ Previous
Next ❯

Citations

Jan 24, 2012·Acta Pharmacologica Sinica·X Edward ZhouH Eric Xu
Feb 14, 2012·Proceedings of the National Academy of Sciences of the United States of America·Yashodhan ChinchorePatrick J Dolph
May 22, 2013·Proceedings of the National Academy of Sciences of the United States of America·Hormoz MoavenJeannie Chen
Sep 13, 2007·The Journal of Biological Chemistry·Sergey A VishnivetskiyVsevolod V Gurevich
Feb 14, 2009·PLoS Genetics·Yashodhan ChinchorePatrick J Dolph
May 1, 2013·The Journal of Biological Chemistry·Rabia U MalikSivaraj Sivaramakrishnan
Dec 5, 2013·Human Molecular Genetics·Mònica AguilàMichael E Cheetham
Oct 17, 2007·Molekuliarnaia biologiia·E R GrinbergE K Khusnutdinova
Mar 20, 2012·Neurobiology of Disease·Ronald D Kinser, Patrick J Dolph
Sep 10, 2011·Pharmacology & Therapeutics·Eugenia V GurevichVsevolod V Gurevich
Jun 21, 2015·Experimental Eye Research·Péter LőrinczGábor Juhász
Sep 3, 2010·Journal of Neurochemistry·François Paquet-DurandPer Ekström

❮ Previous
Next ❯

Methods Mentioned

BETA
immunoprecipitation
transfection
transgenic

Software Mentioned

Adobe Photoshop

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.