Journal ArticleDOI
Vacuolar ATPases: rotary proton pumps in physiology and pathophysiology.
TLDR
The acidity of intracellular compartments and the extracellular environment is crucial to various cellular processes, including membrane trafficking, protein degradation, bone resorption and sperm maturation, and the V-ATPases represent attractive and potentially highly specific drug targets.Abstract:
The acidity of intracellular compartments and the extracellular environment is crucial to various cellular processes, including membrane trafficking, protein degradation, bone resorption and sperm maturation. At the heart of regulating acidity are the vacuolar (V-)ATPases--large, multisubunit complexes that function as ATP-driven proton pumps. Their activity is controlled by regulating the assembly of the V-ATPase complex or by the dynamic regulation of V-ATPase expression on membrane surfaces. The V-ATPases have been implicated in a number of diseases and, coupled with their complex isoform composition, represent attractive and potentially highly specific drug targets.read more
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A SARS-CoV-2 protein interaction map reveals targets for drug repurposing.
David E. Gordon,Gwendolyn M. Jang,Mehdi Bouhaddou,Jiewei Xu,Kirsten Obernier,Kris M. White,Matthew J. O’Meara,Veronica V. Rezelj,Jeffrey Z. Guo,Danielle L. Swaney,Tia A. Tummino,Ruth Hüttenhain,Robyn M. Kaake,Alicia L. Richards,Beril Tutuncuoglu,Helene Foussard,Jyoti Batra,Kelsey M. Haas,Maya Modak,Minkyu Kim,Paige Haas,Benjamin J. Polacco,Hannes Braberg,Jacqueline M. Fabius,Manon Eckhardt,Margaret Soucheray,Melanie J. Bennett,Merve Cakir,Michael McGregor,Qiongyu Li,Bjoern Meyer,Ferdinand Roesch,Thomas Vallet,Alice Mac Kain,Lisa Miorin,Elena Moreno,Zun Zar Chi Naing,Yuan Zhou,Shiming Peng,Ying Shi,Ziyang Zhang,Wenqi Shen,Ilsa T Kirby,James E. Melnyk,John S. Chorba,Kevin Lou,Shizhong Dai,Inigo Barrio-Hernandez,Danish Memon,Claudia Hernandez-Armenta,Jiankun Lyu,Christopher J.P. Mathy,Tina Perica,Kala Bharath Pilla,Sai J. Ganesan,Daniel J. Saltzberg,Rakesh Ramachandran,Xi Liu,Sara Brin Rosenthal,Lorenzo Calviello,Srivats Venkataramanan,Jose Liboy-Lugo,Yizhu Lin,Xi Ping Huang,Yongfeng Liu,Stephanie A. Wankowicz,Markus Bohn,Maliheh Safari,Fatima S. Ugur,Cassandra Koh,Nastaran Sadat Savar,Quang Dinh Tran,Djoshkun Shengjuler,Sabrina J. Fletcher,Michael C. O’Neal,Yiming Cai,Jason C.J. Chang,David J. Broadhurst,Saker Klippsten,Phillip P. Sharp,Nicole A. Wenzell,Duygu Kuzuoğlu-Öztürk,Hao-Yuan Wang,Raphael Trenker,Janet M. Young,Devin A. Cavero,Devin A. Cavero,Joseph Hiatt,Joseph Hiatt,Theodore L. Roth,Ujjwal Rathore,Ujjwal Rathore,Advait Subramanian,Julia Noack,Mathieu Hubert,Robert M. Stroud,Alan D. Frankel,Oren S. Rosenberg,Kliment A. Verba,David A. Agard,Melanie Ott,Michael Emerman,Natalia Jura,Mark von Zastrow,Eric Verdin,Eric Verdin,Alan Ashworth,Olivier Schwartz,Christophe d'Enfert,Shaeri Mukherjee,Matthew P. Jacobson,Harmit S. Malik,Danica Galonić Fujimori,Trey Ideker,Charles S. Craik,Stephen N. Floor,James S. Fraser,John D. Gross,Andrej Sali,Bryan L. Roth,Davide Ruggero,Jack Taunton,Tanja Kortemme,Pedro Beltrao,Marco Vignuzzi,Adolfo García-Sastre,Kevan M. Shokat,Brian K. Shoichet,Nevan J. Krogan +128 more
TL;DR: A human–SARS-CoV-2 protein interaction map highlights cellular processes that are hijacked by the virus and that can be targeted by existing drugs, including inhibitors of mRNA translation and predicted regulators of the sigma receptors.
Journal ArticleDOI
Endosome maturation: Endosome maturation
Jatta Huotari,Ari Helenius +1 more
TL;DR: The maturation programme entails a dramatic transformation of these dynamic organelles disconnecting them functionally and spatially from early endosomes and preparing them for their unidirectional role as a feeder pathway to lysosomes.
Journal ArticleDOI
Sensors and regulators of intracellular pH
TL;DR: A dynamic, finely tuned balance between proton-extruding andProton-importing processes underlies pH homeostasis not only in the cytosol, but in other cellular compartments as well.
Journal ArticleDOI
mTORC1 Senses Lysosomal Amino Acids Through an Inside-Out Mechanism That Requires the Vacuolar H+-ATPase
TL;DR: In this article, the v-ATPase engages in extensive amino acid-sensitive interactions with the Ragulator, a scaffolding complex that anchors the Rag GTPases to the lysosome.
mTORC1 Senses Lysosomal Amino Acids Through an Inside-Out Mechanism That Requires the Vacuolar H+-ATPase
TL;DR: The v-ATPase is identified as a component of the mTOR pathway and a lysosome-associated machinery for amino acid sensing is delineated, suggesting that amino acid signaling begins within the lysOSomal lumen.
References
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Journal ArticleDOI
The vacuolar (H+)-ATPases--nature's most versatile proton pumps.
Tsuyoshi Nishi,Michael Forgac +1 more
TL;DR: The pH of intracellular compartments in eukaryotic cells is a carefully controlled parameter that affects many cellular processes, including intrACEllular membrane transport, prohormone processing and transport of neurotransmitters, as well as the entry of many viruses into cells.
Journal ArticleDOI
ATP synthase--a marvellous rotary engine of the cell.
TL;DR: The mechanisms by which rotation and catalysis are coupled in the working enzyme are now being unravelled on a molecular scale.
Journal ArticleDOI
Activation of lysosomal function during dendritic cell maturation.
TL;DR: Lysosomal function in DCs appears to be specialized for the developmentally regulated processing of internalized antigens in the formation of peptide–MHC class II complexes.
Journal ArticleDOI
Mutations in the gene encoding B1 subunit of H+-ATPase cause renal tubular acidosis with sensorineural deafness
Fiona E. Karet,Karin E. Finberg,Raoul D. Nelson,Ahmet Nayir,H Mocan,Sami A. Sanjad,Juan Rodriguez-Soriano,Fernando Santos,Cwrj Cremers,A. di Pietro,BI Hoffbrand,J Winiarski,Aysin Bakkaloglu,Seza Ozen,Ruhan Düşünsel,P Goodyer,Sally A. Hulton,Doris K. Wu,Anne B. Skvorak,Cynthia C. Morton,Michael J. Cunningham,[No Value] Jha,Richard P. Lifton +22 more
TL;DR: It is demonstrated that mutations in ATP6B1, encoding the B-subunit of the apical proton pump mediating distal nephron acid secretion, cause distal renal tubular acidosis, a condition characterized by impaired renal acid secretion resulting in metabolic acidosis.
Journal ArticleDOI
Defects in TCIRG1 subunit of the vacuolar proton pump are responsible for a subset of human autosomal recessive osteopetrosis.
Annalisa Frattini,Paul J. Orchard,Cristina Sobacchi,Silvia Giliani,Mario Abinun,Jan P. Mattsson,David J. Keeling,Ann Katrin Andersson,Pia Wallbrandt,Luigi Zecca,Luigi D. Notarangelo,Paolo Vezzoni,Anna Villa +12 more
TL;DR: It is shown that TCIRG1, encoding the osteoclast-specific 116-kD subunit of the vacuolar proton pump, is mutated in five of nine patients with a diagnosis of infantile malignant osteopetrosis, indicating that mutations in TC IRG1 are a frequent cause of autosomal recessive osteopeterosis in humans.
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