Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Jun 24:9:670882.
doi: 10.3389/fcell.2021.670882. eCollection 2021.

F-Actin Dynamics in the Regulation of Endosomal Recycling and Immune Synapse Assembly

Nagaja Capitani  1 , Cosima T Baldari  1
Affiliations
Review

F-Actin Dynamics in the Regulation of Endosomal Recycling and Immune Synapse Assembly

Nagaja Capitani et al. Front Cell Dev Biol. .

Abstract

Membrane proteins endocytosed at the cell surface as vesicular cargoes are sorted at early endosomes for delivery to lysosomes for degradation or alternatively recycled to different cellular destinations. Cargo recycling is orchestrated by multimolecular complexes that include the retromer, retriever, and the WASH complex, which promote the polymerization of new actin filaments at early endosomes. These endosomal actin pools play a key role at different steps of the recycling process, from cargo segregation to specific endosomal subdomains to the generation and mobility of tubulo-vesicular transport carriers. Local F-actin pools also participate in the complex redistribution of endomembranes and organelles that leads to the acquisition of cell polarity. Here, we will present an overview of the contribution of endosomal F-actin to T-cell polarization during assembly of the immune synapse, a specialized membrane domain that T cells form at the contact with cognate antigen-presenting cells.

Keywords: WASH complex; actin dynamics; endosome; polarized recycling; retriever; retromer; vesicular trafficking.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Overview of endosomal sorting and associated molecular machineries. (A) Following internalization, transmembrane proteins can be delivered to the degradative pathway through late endosomes and finally lysosomes or can be destined for recycling. Delivery of cargo back to the cell surface can occur directly through the fast recycling pathway or indirectly through the slow recycling pathway involving the pericentrosomal recycling compartment. Some cargo proteins can undergo retrograde transport from endosome to the Trans Golgi Network (TGN). (B,C) Multiprotein complexes involved in the retrieval and recycling of cargo proteins on (B) endosomes and the (C) components of each complex.
FIGURE 2
FIGURE 2
Recycling of receptors through actin-rich tubular domains. Sequence-dependent recycling of cargoes is tightly regulated by actin dynamics at the surface of endosomes. The retrieving machineries (retromer or retriever), together with the WASH complex, allow for the entry of the receptors into tubular profiles enriched in F-actin and actin-related proteins. Microtubule motors drive the stabilization and extension of the tubular profiles and branched F-actin contributes to vesicle fission.
FIGURE 3
FIGURE 3
Vesicular trafficking in the regulation of IS formation. Upon TCR stimulation, the T-cell receptor, as well as associated signaling molecules (e.g., LAT and Lck), are delivered to the IS via endosomal vesicles. The polarized trafficking of different molecules occurs through distinct trafficking routes within the “classical” recycling pathway regulated by the Rab5 and Rab11. TCR-polarized trafficking to the IS involves additional Rab GTPases, some components of the intraflagellar transport (IFT) system, and the ciliogenesis protein CCDC28B that is essential for WAS-dependent actin polymerization on TCR+ endosomes. Lck associates with Rab11+ endosomal compartments, and its transport to the IS and sorting to the cSMAC are regulated by the uncoordinated 119 protein (Unc119), the membrane protein MAL, and Rab11-FIP3. LAT trafficking to the IS occurs through the classical Rab5 and Rab11 route, where anterograde transport is specifically regulated by GMAP210, IFT20, and VAMP7 and retrograde transport by Rab6 and Syntaxin-16.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Alcover A., Alarcón B., Di Bartolo V. (2018). Cell biology of T cell receptor expression and regulation. Annu. Rev. Immunol. 36 103–125. 10.1146/annurev-immunol-042617-053429 - DOI - PubMed
    1. Alekhina O., Burstein E., Billadeau D. D. (2017). Cellular functions of WASP family proteins at a glance. J. Cell Sci. 130 2235–2241. 10.1242/jcs.199570 - DOI - PMC - PubMed
    1. Andrés-Delgado L., Antón O.-M., Madrid R., Byrne J. A., Alonso M. A. (2010). Formin INF2 regulates MAL-mediated transport of Lck to the plasma membrane of human T lymphocytes. Blood 116 5919–5929. 10.1182/blood-2010-08-300665 - DOI - PubMed
    1. Antón O. M., Andrés-Delgado L., Reglero-Real N., Batista A., Alonso M. A. (2011). MAL protein controls protein sorting at the supramolecular activation cluster of human T lymphocytes. J. Immunol. 186 6345–6356. 10.4049/jimmunol.1003771 - DOI - PubMed
    1. Bartuzi P., Billadeau D. D., Favier R., Rong S., Dekker D., Fedoseienko A., et al. (2016). CCC- and WASH-mediated endosomal sorting of LDLR is required for normal clearance of circulating LDL. Nat. Commun. 7:10961. 10.1038/ncomms10961 - DOI - PMC - PubMed

LinkOut - more resources