Kay, R.R. orcid.org/0000-0001-9836-7967, Lutton, J.E., King, J.S. orcid.org/0000-0003-0596-4506 et al. (1 more author) (2024) Making cups and rings: the ‘stalled-wave’ model for macropinocytosis. Biochemical Society Transactions, 52 (4). pp. 1785-1794. ISSN 0300-5127
Abstract
Macropinocytosis is a broadly conserved endocytic process discovered nearly 100 years ago, yet still poorly understood. It is prominent in cancer cell feeding, immune surveillance, uptake of RNA vaccines and as an invasion route for pathogens. Macropinocytic cells extend large cups or flaps from their plasma membrane to engulf droplets of medium and trap them in micron-sized vesicles. Here they are digested and the products absorbed. A major problem — discussed here — is to understand how cups are shaped and closed. Recently, lattice light-sheet microscopy has given a detailed description of this process in Dictyostelium amoebae, leading to the ‘stalled-wave’ model for cup formation and closure. This is based on membrane domains of PIP3 and active Ras and Rac that occupy the inner face of macropinocytic cups and are readily visible with suitable reporters. These domains attract activators of dendritic actin polymerization to their periphery, creating a ring of protrusive F-actin around themselves, thus shaping the walls of the cup. As domains grow, they drive a wave of actin polymerization across the plasma membrane that expands the cup. When domains stall, continued actin polymerization under the membrane, combined with increasing membrane tension in the cup, drives closure at lip or base. Modelling supports the feasibility of this scheme. No specialist coat proteins or contractile activities are required to shape and close cups: rings of actin polymerization formed around PIP3 domains that expand and stall seem sufficient. This scheme may be widely applicable and begs many biochemical questions.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2024 The Author(s). This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY) https://creativecommons.org/licenses/by/4.0/ |
Keywords: | Dictyostelium discoideum; PIP3; cytoskeleton; endocytosis; macropinocytosis; Pinocytosis; Dictyostelium; Cell Membrane; Humans; Actins; Animals; Models, Biological |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) |
Funding Information: | Funder Grant number BIOTECHNOLOGY AND BIOLOGICAL SCIENCES RESEARCH COUNCIL BB/M012522/1 ROYAL SOCIETY URF\R\201036 UK RESEARCH AND INNOVATION BB/X003329/1 ROYAL SOCIETY UF140624 ROYAL SOCIETY RG150439/revised letter BIOTECHNOLOGY AND BIOLOGICAL SCIENCES RESEARCH COUNCIL BB/W002760/1 Medical Research Council 1947310 ROYAL SOCIETY RG130655 MEDICAL RESEARCH COUNCIL MC_PC_ APP28599 ROYAL SOCIETY RGF\EA\180126 BIOTECHNOLOGY AND BIOLOGICAL SCIENCES RESEARCH COUNCIL BB/W006049/1 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 31 Jan 2025 16:13 |
Last Modified: | 31 Jan 2025 16:13 |
Status: | Published |
Publisher: | Portland Press Ltd. |
Refereed: | Yes |
Identification Number: | 10.1042/bst20231426 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:222486 |
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