Distinct Arp2/3 isocomplexes drive axonal actin ring assembly and integrity

The actin-related protein 2/3 (Arp2/3) complex is a central nucleator of branched actin filaments, essential for numerous cellular processes. Using superresolution imaging, we demonstrate that Arp2/3 is a component of the membrane periodic skeleton (MPS)—a highly ordered actin ring-spectrin lattice in the submembrane axonal cytoskeleton. While generally viewed as a single entity, functional specialization of the Arp2/3 complex arises from isoform diversity of three of its seven subunits. Moreover, isoform-specific perturbations revealed that distinct Arp2/3 isocomplexes orchestrate successive stages of MPS actin ring development. While Arp2/3 isocomplexes containing ARPC1A and ARPC5 are essential for actin ring assembly during early MPS formation, those with ARPC1B and ARPC5L are key to maintaining actin rings in mature axons. These findings demonstrate that beyond linear actin, branched actin filaments contribute to the MPS nanoarchitecture and uncover a switch in Arp2/3 isocomplex composition that is required to ensure actin ring assembly and stability.

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Publication Details

Journal
Science Advances
Published
2026-09-25
DOI
https://doi.org/10.1126/sciadv.aec9522
Primary Topic
Cellular Mechanics and Interactions
Type
article
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article

Distinct Arp2/3 isocomplexes drive axonal actin ring assembly and integrity

Marko Lampe, Paulo Aguiar, Michael Way, Christoph K. Spahn et al.
Science Advances
Cellular Mechanics and Interactions
article

Distinct Arp2/3 isocomplexes drive axonal actin ring assembly and integrity

Marko Lampe, Paulo Aguiar, Michael Way, Christoph K. Spahn, Maria Leonor Moura, Paula Sampaio, José C. Mateus, Mónica Mendes Sousa, Ana Rita Costa, Naoko Kogata, Luís P. Rodrigues, Pedro Brites, António J. Pereira, João M. Rocha, Teresa Lopes
article en

Abstract

The actin-related protein 2/3 (Arp2/3) complex is a central nucleator of branched actin filaments, essential for numerous cellular processes. Using superresolution imaging, we demonstrate that Arp2/3 is a component of the membrane periodic skeleton (MPS)—a highly ordered actin ring-spectrin lattice in the submembrane axonal cytoskeleton. While generally viewed as a single entity, functional specialization of the Arp2/3 complex arises from isoform diversity of three of its seven subunits. Moreover, isoform-specific perturbations revealed that distinct Arp2/3 isocomplexes orchestrate successive stages of MPS actin ring development. While Arp2/3 isocomplexes containing ARPC1A and ARPC5 are essential for actin ring assembly during early MPS formation, those with ARPC1B and ARPC5L are key to maintaining actin rings in mature axons. These findings demonstrate that beyond linear actin, branched actin filaments contribute to the MPS nanoarchitecture and uncover a switch in Arp2/3 isocomplex composition that is required to ensure actin ring assembly and stability.

Science AdvancesVol. 12(39)
German Cancer Research Center (DE), Heidelberg University (DE), University of Würzburg (DE), The Francis Crick Institute (GB), European Molecular Biology Laboratory (DE), i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto (PT), Imperial College London (GB), University of Minho (PT)
Openalex Percentile: Top 15%
Cellular Mechanics and Interactions
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