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| http://dx.doi.org/10.1074/jbc.A114.578245 | DOI Listing |
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Mechanism to disrupt ESCRT-mediated intracellular trafficking through Vps28-small molecules interaction: an in silico approach.
J Biomol Struct Dyn
December 2024
Department of Biochemistry, Central University of Haryana, Mahendergarh, Haryana, India.
The ESCRT (Endosomal Sorting Complex Required for Transport) machinery comprising protein complexes ESCRT-0 to ESCRT-III and Vps4 plays a pivotal role in intracellular trafficking, a process of endocytosing cell surface proteins into the cell for various biological activities. The ESCRT protein complexes are sequentially assembled which interact amongst each other to form a functional ESCRT machinery. Deregulation of these events are shown to be involved in various disease development including tumor formation and viral infections.
View Article and Find Full Text PDFRapid turnover of CTLA4 is associated with a complex architecture of reversible ubiquitylation.
J Cell Biol
January 2025
Biochemistry, Cell and Systems Biology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK.
Article Synopsis
- - The immune checkpoint protein CTLA4 has a short lifespan and is degraded in lysosomes through a process involving ubiquitylation at specific lysine residues.
- - Inhibition of a specific cellular pump (v-ATPase) can raise CTLA4 levels, and some CTLA4 is found in exosomes, indicating it can be secreted out of cells.
- - The deubiquitylase enzyme USP8 helps regulate CTLA4 levels; losing USP8 leads to increased ubiquitylation and affects how CTLA4 accumulates in cells and exosomes, with distinct implications for its degradation process.
Analysis of the neuromuscular deficits caused by STAM1 deficiency.
Curr Res Neurobiol
August 2024
Department of Neurobiology, Evelyn F. McKnight Brain Institute, Civitan International Research Center, University of Alabama at Birmingham, Birmingham, 35294, Alabama, USA.
The endosomal sorting complexes required for transport (ESCRT) pathway is composed of a series of protein complexes that are essential for sorting cargo through the endosome. In neurons, the ESCRT pathway is a key mediator of many cellular pathways that regulate neuronal morphogenesis as well as synaptic growth and function. The ESCRT-0 complex, consisting of HGS (hepatocyte growth factor-regulated tyrosine kinase substrate) and STAM (signal-transducing adaptor molecule), acts as a gate keeper to this pathway, ultimately determining the fate of the endosomal cargo.
View Article and Find Full Text PDFAn internal linker and pH biosensing by phosphatidylinositol 5-phosphate regulate the function of the ESCRT-0 component TOM1.
Structure
October 2024
Protein Signaling Domains Laboratory, Department of Biological Sciences, Fralin Life Sciences Institute, and Center for Soft Matter and Biological Physics, Virginia Tech, Blacksburg, VA 24061, USA. Electronic address:
Article Synopsis
- - The study explores how Target of Myb1 (TOM1) helps transport ubiquitinated proteins to lysosomes for degradation, revealing that a specific region near TOM1 enhances its binding to ubiquitin and can be altered through phosphorylation.
- - Researchers found that TOM1 acts as an effector for a lipid called phosphatidylinositol 5-phosphate (PtdIns5P) during infections from Shigella flexneri, with its binding to PtdIns5P being influenced by pH levels.
- - The findings suggest that during Shigella infection, the acidic environment affects TOM1's ability to bind ubiquitin, which hinders endosomal maturation and protein degradation, thus aiding bacterial survival by accumulating TOM1
Modulation of abscisic acid signaling via endosomal TOL proteins.
New Phytol
August 2024
Department of Applied Genetics and Cell Biology, Institute of Molecular Plant Biology, BOKU University, Muthgasse 18, 1190, Vienna, Austria.
The phytohormone abscisic acid (ABA) functions in the control of plant stress responses, particularly in drought stress. A significant mechanism in attenuating and terminating ABA signals involves regulated protein turnover, with certain ABA receptors, despite their main presence in the cytosol and nucleus, subjected to vacuolar degradation via the Endosomal Sorting Complex Required for Transport (ESCRT) machinery. Collectively our findings show that discrete TOM1-LIKE (TOL) proteins, which are functional ESCRT-0 complex substitutes in plants, affect the trafficking for degradation of core components of the ABA signaling and transport machinery.
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