ClC-7 requires Ostm1 as a beta-subunit to support bone resorption and lysosomal function

Nature
Philipp F LangeJens C Fuhrmann

Abstract

Mutations in ClC-7, a late endosomal/lysosomal member of the CLC family of chloride channels and transporters, cause osteopetrosis and lysosomal storage disease in humans and mice. Severe osteopetrosis is also observed with mutations in the OSTM1 gene, which encodes a membrane protein of unknown function. Here we show that both ClC-7 and Ostm1 proteins co-localize in late endosomes and lysosomes of various tissues, as well as in the ruffled border of bone-resorbing osteoclasts. Co-immunoprecipitations show that ClC-7 and Ostm1 form a molecular complex and suggest that Ostm1 is a beta-subunit of ClC-7. ClC-7 is required for Ostm1 to reach lysosomes, where the highly glycosylated Ostm1 luminal domain is cleaved. Protein but not RNA levels of ClC-7 are greatly reduced in grey-lethal mice, which lack Ostm1, suggesting that the ClC-7-Ostm1 interaction is important for protein stability. As ClC-7 protein levels in Ostm1-deficient tissues and cells, including osteoclasts, are decreased below 10% of normal levels, Ostm1 mutations probably cause osteopetrosis by impairing the acidification of the osteoclast resorption lacuna, which depends on ClC-7 (ref. 3). The finding that grey-lethal mice, just like ClC-7-deficient mice, show lysosom...Continue Reading

References

Mar 2, 1999·Mammalian Genome : Official Journal of the International Mammalian Genome Society·J Vacher, H Bernard
Jun 8, 2001·Annual Review of Biochemistry·C M Pickart
Mar 12, 2003·Trends in Cell Biology·Eeva-Liisa EskelinenPaul Saftig
Apr 2, 2003·Nature Medicine·Brendan F Boyce
Jun 27, 2003·Proceedings of the National Academy of Sciences of the United States of America·Thierry FischerMarilyn Gist Farquhar
Oct 31, 2003·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Annalisa FrattiniAnna Villa
Feb 27, 2004·Nature·Alessio Accardi, Christopher Miller
Jun 5, 2004·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Paola QuarelloUgo Ramenghi
Feb 12, 2005·The EMBO Journal·Dagmar KasperThomas J Jentsch
Feb 16, 2005·Annual Review of Physiology·Thomas J JentschAnselm A Zdebik
May 26, 2005·Current Opinion in Neurobiology·Thomas J JentschOlaf Scheel
Jul 22, 2005·Nature·Alessandra Picollo, Michael Pusch

❮ Previous
Next ❯

Citations

Oct 30, 2008·Calcified Tissue International·Anita Vibsig Neutzsky-WulffKim Henriksen
Dec 17, 2008·Calcified Tissue International·Anna VillaCristina Sobacchi
Oct 15, 2008·Pflügers Archiv : European journal of physiology·Vanessa PlansThomas J Jentsch
Jan 6, 2010·Pflügers Archiv : European journal of physiology·Leigh WellhauserChristine E Bear
Nov 7, 2008·Human Genetics·T Segovia-SilvestreK Henriksen
Nov 3, 2010·Journal of Bone and Mineral Metabolism·Ping YuanYiming Wang
Apr 22, 2008·Journal of Inherited Metabolic Disease·C Sagné, B Gasnier
Sep 11, 2008·Glycoconjugate Journal·Alessandro PrinettiSandro Sonnino
May 19, 2009·Nature Medicine·Thorsten SchinkeMichael Amling
Dec 19, 2009·Proceedings of the National Academy of Sciences of the United States of America·R W FriddleJ J De Yoreo
Jan 7, 2010·The Journal of Biological Chemistry·Patricia PrestonThomas J Jentsch
May 15, 2010·The Journal of Biological Chemistry·Ioana NeagoeThomas J Jentsch
Sep 8, 2010·The Journal of Biological Chemistry·Tobias Stauber, Thomas J Jentsch
Sep 16, 2008·The Journal of Biological Chemistry·Monica PataJean Vacher
Jan 13, 2009·The Journal of Biological Chemistry·Peter M Haggie, A S Verkman
Mar 6, 2009·The Journal of Biological Chemistry·Eun-Yeong BergsdorfThomas J Jentsch
Mar 16, 2011·The Journal of General Physiology·Jessica E DiCiccio, Benjamin E Steinberg
May 29, 2013·The Journal of General Physiology·Yoichi IshidaMichael Grabe
Mar 29, 2011·Molecular Biology of the Cell·Amitabha MajumdarFrederick R Maxfield
Aug 18, 2006·Current Opinion in Nephrology and Hypertension·Saba SileAlfred L George
Mar 31, 2009·American Journal of Physiology. Lung Cellular and Molecular Physiology·Peter M Haggie, A S Verkman
Apr 4, 2007·The Journal of Clinical Investigation·Liesbeth Van WesenbeeckWim Van Hul
Dec 18, 2013·Laboratory Investigation; a Journal of Technical Methods and Pathology·Amélie E CoudertMarie-Christine de Vernejoul
Sep 5, 2006·Proceedings of the National Academy of Sciences of the United States of America·Mallorie PoëtThomas J Jentsch
Mar 5, 2013·Annual Review of Biophysics·Christof GrewerKlaus Fendler
Oct 25, 2012·Annual Review of Physiology·Tobias Stauber, Thomas J Jentsch
Jul 19, 2014·Archives of Biochemistry and Biophysics·Nicholas W Bellono, Elena V Oancea
Feb 24, 2009·Orphanet Journal of Rare Diseases·Zornitza Stark, Ravi Savarirayan
Feb 18, 2012·Annual Review of Physiology·Joseph A Mindell
Feb 25, 2009·European Journal of Pediatrics·Nesrin BesbasFatih Ozaltin
Jun 23, 2010·The Journal of Cell Biology·Benjamin E SteinbergSergio Grinstein
Feb 19, 2016·International Journal of Rheumatic Diseases·Adam AustinPrashant Kaushik
Nov 6, 2013·FEBS Letters·Andy K M LamSpyros Zissimopoulos
Mar 1, 2008·Critical Reviews in Biochemistry and Molecular Biology·Thomas J Jentsch

❮ 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.

Related Papers

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Lena WartoschThomas J Jentsch
Biochemical and Biophysical Research Communications
Qingxiao ZhaoYongtao Xiao
Pflügers Archiv : European journal of physiology
Vanessa PlansThomas J Jentsch
© 2021 Meta ULC. All rights reserved