Kevin
Lim
Elucidating how Eukaryotic Cells Regulate Organelle pH
Abstract profile. Full document pending author claim.
Authors:
Kevin Lim, Christopher Nardone, Tom Rapoport
Date Created:
2025-01-01
Course Title:
Professor:
Not specified
About Paper:
Vacuolar-type ATPases (V-ATPases) acidify intracellular PI4P. This lipid interaction anchors mRAVE to the membrane organelles like lysosomes, the Golgi apparatus, and synaptic and enables recruitment of V1. Using AlphaFold3, we have vesicles, playing critical roles in cellular degradation, protein identified a conserved, non-canonical plekstrin-homology (PH) trafficking, and neurotransmission. V-ATPases consist of a domain in mRAVE to mediate the interaction with PI4P. Using cytosolically-disposed V1 subcomplex, which hydrolyzes ATP, live cell imaging, we found that mRAVE localizes to the Golgi, and a membrane-embedded V0 subcomplex, which pumps the major site of V-ATPase biosynthesis, likely due to the striking protons. Their assembly is essential for function, but how this enrichment of PI4P in this organelle. Future work aims to process occurs mechanistically and is regulated in human cells determinewhetherbindingtoGolgi-derivedmembranesisrequired remains unclear. The Rapoport lab recently identified mRAVE, a for the acidification of the organelle and plays a critical role in metazoan complex that bridges V1 and V0 when organelle proton protein trafficking. We are also performing cryogenic-electron gradients dissipate, catalyzing their assembly to restore lysosomalmicroscopy to determine an atomic model of the mRAVE-V1 acidification and neurotransmitter loading. mRAVE consists of complex on the membrane. Overall, these findings reveal key WDR7, the central linker ROGDI, and DMXL1/2, which interact mechanistic roles for mRAVE function in V-ATPase assembly, with the inactive V1. Under the guidance of Dr. Christopher furthering our understanding of organelle acidification so that we Nardone, our project aims to elucidate how this mRAVE regulates can develop potential therapeutic interventions for diseases linked V-ATPase assembly. We screened a panel of lipids and found that to defective V-ATPase function, such as neurodegeneration and mRAVE strongly binds to the phosphoinositide PI4P, which we renal tubular acidosis. confirmed through a flotation assay using liposomes containing
Abstract:
Vacuolar-type ATPases (V-ATPases) acidify intracellular PI4P. This lipid interaction anchors mRAVE to the membrane organelles like lysosomes, the Golgi apparatus, and synaptic and enables recruitment of V1. Using AlphaFold3, we have vesicles, playing critical roles in cellular degradation, protein identified a conserved, non-canonical plekstrin-homology (PH) trafficking, and neurotransmission. V-ATPases consist of a domain in mRAVE to mediate the interaction with PI4P. Using cytosolically-disposed V1 subcomplex, which hydrolyzes ATP, live cell imaging, we found that mRAVE localizes to the Golgi, and a membrane-embedded V0 subcomplex, which pumps the major site of V-ATPase biosynthesis, likely due to the striking protons. Their assembly is essential for function, but how this enrichment of PI4P in this organelle. Future work aims to process occurs mechanistically and is regulated in human cells determinewhetherbindingtoGolgi-derivedmembranesisrequired remains unclear. The Rapoport lab recently identified mRAVE, a for the acidification of the organelle and plays a critical role in metazoan complex that bridges V1 and V0 when organelle proton protein trafficking. We are also performing cryogenic-electron gradients dissipate, catalyzing their assembly to restore lysosomalmicroscopy to determine an atomic model of the mRAVE-V1 acidification and neurotransmitter loading. mRAVE consists of complex on the membrane. Overall, these findings reveal key WDR7, the central linker ROGDI, and DMXL1/2, which interact mechanistic roles for mRAVE function in V-ATPase assembly, with the inactive V1. Under the guidance of Dr. Christopher furthering our understanding of organelle acidification so that we Nardone, our project aims to elucidate how this mRAVE regulates can develop potential therapeutic interventions for diseases linked V-ATPase assembly. We screened a panel of lipids and found that to defective V-ATPase function, such as neurodegeneration and mRAVE strongly binds to the phosphoinositide PI4P, which we renal tubular acidosis. confirmed through a flotation assay using liposomes containing
Source:
Harvard / Harvard College | Eliot House | Neuroscience | 2027 / 2025
Topics:
mrave, organelle, pi4p, assembly, cell, membrane, using, role, function, acidification, regulate, lipid
