ESCRT-III executes membrane scission during the budding of intralumenal vesicles (ILVs) at endosomes. The scission mechanism is unknown but appears to be linked to the cycle of assembly and disassembly of ESCRT-III complexes at membranes. Regulating this cycle is therefore expected to be important for determining the timing of ESCRT-III-mediated membrane scission. We show that in , ESCRT-III complexes are stabilized and ILV membrane scission is delayed by Doa4, which is the ubiquitin hydrolase that deubiquitinates transmembrane proteins sorted as cargoes into ILVs. These results suggest a mechanism to delay ILV budding while cargoes undergo deubiquitination. We further show that deubiquitination of ILV cargoes is inhibited via Doa4 binding to Vps20, which is the subunit of ESCRT-III that initiates assembly of the complex. Current models suggest that ESCRT-III complexes surround ubiquitinated cargoes to trap them at the site of ILV budding while the cargoes undergo deubiquitination. Thus our results also propose a mechanism to prevent the onset of ILV cargo deubiquitination at the initiation of ESCRT-III complex assembly.
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http://dx.doi.org/10.1091/mbc.E16-11-0761 | DOI Listing |
Cell Death Differ
December 2024
State Key Laboratory of Microbial Metabolism & Joint International Research Laboratory of Metabolic & Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, PR China.
Autophagosomes are formed by the enlargement and sealing of phagophores. This is accompanied by the recruitment and release of autophagy-related (Atg) proteins that function therein. Presently, the relationship among factors that act after the initial emergence of the phagophore is unclear.
View Article and Find Full Text PDFCell Rep
December 2024
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA. Electronic address:
During clathrin-mediated endocytosis (CME), dozens of proteins are recruited to nascent CME sites on the plasma membrane, and their spatial and temporal coordination is crucial for efficient CME. Here, we show that the scaffold protein intersectin1 (ITSN1) promotes CME by organizing and stabilizing endocytic protein interaction networks. Live-cell imaging of genome-edited cells revealed that endogenously labeled ITSN1 is recruited during CME site stabilization and growth and that ITSN1 knockdown impairs endocytic protein recruitment during this stage.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
November 2024
Membrane Traffic and Cell Division Unit, Institut Pasteur, Université Paris Cité, CNRS UMR3691, Paris F-75015, France.
Many enveloped viruses bud from the plasma membrane that is tightly associated with a dense and thick actin cortex. This actin network represents a significant challenge for membrane deformation and scission, and how it is remodeled during the late steps of the viral cycle is largely unknown. Using superresolution microscopy, we show that HIV-1 buds in areas of the plasma membrane with low cortical F-actin levels.
View Article and Find Full Text PDFJ Chem Theory Comput
November 2024
Laboratory of Medicinal Chemistry, Section of Pharmaceutical Chemistry, Department of Pharmacy, National and Kapodistrian University of Athens, Panepistimiopolis Zografou, Athens 15771, Greece.
The influenza A M2 homotetrameric channel consists of four transmembrane (TM) and four amphipathic helices (AHs). This viral proton channel is suggested to form clusters in the catenoid budding neck areas in raft-like domains of the plasma membrane, resulting in cell membrane scission and viral release. The channel clustering environment is rich in cholesterol.
View Article and Find Full Text PDFJ Neurosci
December 2024
Department of Otolaryngology, Stanford University, Stanford, California
Mutations in human are associated with neurodevelopmental defects, including motor delays and defective muscle tone. encodes a AAA-ATPase required for membrane scission, but how mutations in lead to impaired control of motor function is not known. Here we identified a mutation in zebrafish , T248I, that affects sensorimotor transformation.
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