Light-responsive microRNA miR-211 targets Ezrin to modulate lysosomal biogenesis and retinal cell clearance.

The EMBO Journal
Federica NasoIvan Conte

Abstract

Vertebrate vision relies on the daily phagocytosis and lysosomal degradation of photoreceptor outer segments (POS) within the retinal pigment epithelium (RPE). However, how these events are controlled by light is largely unknown. Here, we show that the light-responsive miR-211 controls lysosomal biogenesis at the beginning of light-dark transitions in the RPE by targeting Ezrin, a cytoskeleton-associated protein essential for the regulation of calcium homeostasis. miR-211-mediated down-regulation of Ezrin leads to Ca2+ influx resulting in the activation of calcineurin, which in turn activates TFEB, the master regulator of lysosomal biogenesis. Light-mediated induction of lysosomal biogenesis and function is impaired in the RPE from miR-211-/- mice that show severely compromised vision. Pharmacological restoration of lysosomal biogenesis through Ezrin inhibition rescued the miR-211-/- phenotype, pointing to a new therapeutic target to counteract retinal degeneration associated with lysosomal dysfunction.

References

Dec 30, 1999·The Journal of Cell Biology·V L BonilhaE Rodriguez-Boulan
Sep 25, 2002·Proceedings of the National Academy of Sciences of the United States of America·Sylvie CoscoyFrançis Amblard
Jun 16, 2004·Proceedings of the National Academy of Sciences of the United States of America·Huiren ZhaoJerrold R Turner
Jun 24, 2004·Nature Reviews. Genetics·Lin He, Gregory J Hannon
Jul 1, 2005·Physiological Reviews·Olaf Strauss
Aug 16, 2006·Proceedings of the National Academy of Sciences of the United States of America·Lars-Peter ErwigPeter M Henson
Oct 10, 2006·Clinical & Experimental Metastasis·Kartik KrishnanLee J Helman
Jan 15, 2008·Advances in Experimental Medicine and Biology·Emeline F NandrotSilvia C Finnemann
May 17, 2008·Journal of Applied Toxicology : JAT·Bruce Ira GaynesJay Perlman
Feb 25, 2009·International Journal of Cancer. Journal International Du Cancer·Cristina FedericiStefano Fais
Jul 10, 2009·International Journal of Cancer. Journal International Du Cancer·Daria Brambilla, Stefano Fais
Jan 9, 2010·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Fei E WangSheldon S Miller
Mar 24, 2010·Nature Reviews. Molecular Cell Biology·Richard G FehonAnthony Bretscher
Dec 22, 2010·BMC Genomics·Marianthi KaraliSandro Banfi
Feb 19, 2011·Investigative Ophthalmology & Visual Science·Alice E DavidsonForbes D C Manson
May 12, 2011·PloS One·Zhenyang ZhaoJiyang Cai
May 28, 2011·Science·Carmine SettembreAndrea Ballabio
Jan 23, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Neetha ParameswaranNeetu Gupta
Jul 23, 2013·Cell·Ji-Young KimThomas A Ferguson
May 1, 2012·Pharmaceutical Patent Analyst·Khrishen CunnusamyShusheng Wang
Dec 4, 2013·Methods in Cell Biology·Elena V Polishchuk, Roman S Polishchuk
Apr 16, 2014·Experimental Eye Research·Lawrence J Rizzolo
May 2, 2014·Investigative Ophthalmology & Visual Science·Jingyu YaoDavid N Zacks
May 9, 2014·Experimental Eye Research·Laura S FrostKathleen Boesze-Battaglia

❮ Previous
Next ❯

Citations

Aug 25, 2020·Oxidative Medicine and Cellular Longevity·Zi-Yuan ZhangGuang-Yu Li
Feb 3, 2021·International Journal of Molecular Sciences·Yue RuanAdrian Gericke
Feb 2, 2021·Frontiers in Cell and Developmental Biology·Daniela IntartagliaIvan Conte
May 17, 2021·The FEBS Journal·Daniela IntartagliaIvan Conte

❮ 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.