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Cited by 719

The DOI matches its Crossref record; 48 of the 48 references it cites were found in a registry or an index.

Formation and release of arrestin domain-containing protein 1-mediated microvesicles (ARMMs) at plasma membrane by recruitment of TSG101 protein

Open access
Nabhan, Joseph F., Hu, Ruoxi, Oh, Raymond S., Cohen, Stanley N., Lu, Quan·2012·Proceedings of the National Academy of Sciences

Abstract

Mammalian cells are capable of delivering multiple types of membrane capsules extracellularly. The limiting membrane of late endosomes can fuse with the plasma membrane, leading to the extracellular release of multivesicular bodies (MVBs), initially contained within the endosomes, as exosomes. Budding viruses exploit the TSG101 protein and endosomal sorting complex required for transport (ESCRT) machinery used for MVB formation to mediate the egress of viral particles from host cells. Here we report the discovery of a virus-independent cellular process that generates microvesicles that are distinct from exosomes and which, like budding viruses, are produced by direct plasma membrane budding. Such budding is driven by a specific interaction of TSG101 with a tetrapeptide PSAP motif of an accessory protein, arrestin domain-containing protein 1 (ARRDC1), which we show is localized to the plasma membrane through its arrestin domain. This interaction results in relocation of TSG101 from endosomes to the plasma membrane and mediates the release of microvesicles that contain TSG101, ARRDC1, and other cellular proteins. Unlike exosomes, which are derived from MVBs, ARRDC1-mediated microvesicles (ARMMs) lack known late endosomal markers. ARMMs formation requires VPS4 ATPase and is enhanced by the E3 ligase WWP2, which interacts with and ubiquitinates ARRDC1. ARRDC1 protein discharged into ARMMs was observed in co-cultured cells, suggesting a role for ARMMs in intercellular communication. Our findings reveal an intrinsic cellular mechanism that results in direct budding of microvesicles from the plasma membrane, providing a formal paradigm for the evolutionary recruitment of ESCRT proteins in the release of budding viruses.

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Metadata

Authors
Nabhan, J. F., Hu, R., Oh, R. S., Cohen, S. N., & Lu, Q.
Venue
Proceedings of the National Academy of Sciences
Published
2012-02-06
Volume
109
Issue
11
Pages
4146-4151
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W1998307755
Cited by
719
References
48
FWCI
11.15
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: Formation and release of arrestin domain-containing protein 1-mediated microvesicles (ARMMs) at plasma membrane by recruitment of TSG101 protein. https://app.cochat.ai/papers/10.1073/pnas.1200448109
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Nabhan, J. F., Hu, R., Oh, R. S., Cohen, S. N., & Lu, Q. (2012). Formation and release of arrestin domain-containing protein 1-mediated microvesicles (ARMMs) at plasma membrane by recruitment of TSG101 protein. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.1200448109

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