Cited by 102Cellular transport and secretionProtein Kinase Regulation and GTPase SignalingCaveolin-1 and cellular processes

Protein complexes containing CYFIP/Sra/PIR121 coordinate Arf1 and Rac1 signalling during clathrin–AP-1-coated carrier biogenesis at the TGN

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Anitei, Mihaela, Stange, Christoph, Parshina, Irina, Baust, Thorsten, Schenck, Annette, Raposo, Graça, Kirchhausen, Tomas, Hoflack, Bernard·2010·Nature Cell Biology

Abstract

Actin dynamics is a tightly regulated process involved in various cellular events including biogenesis of clathrin-coated, AP-1 (adaptor protein 1)-coated transport carriers connecting the trans-Golgi network (TGN) and the endocytic pathway. However, the mechanisms coordinating coat assembly, membrane and actin remodelling during post-TGN transport remain poorly understood. Here we show that the Arf1 (ADP-ribosylation factor 1) GTPase synchronizes the TGN association of clathrin-AP-1 coats and protein complexes comprising CYFIP (cytoplasmic fragile-X mental retardation interacting protein; Sra, PIR121), a clathrin heavy chain binding protein associated with mental retardation. The Rac1 GTPase and its exchange factor beta-PIX (PAK-interacting exchange factor) activate these complexes, allowing N-WASP-dependent and Arp2/3-dependent actin polymerization towards membranes, thus promoting tubule formation. These phenomena can be recapitulated with synthetic membranes. This protein-network-based mechanism facilitates the sequential coordination of Arf1-dependent membrane priming, through the recruitment of coats and CYFIP-containing complexes, and of Rac1-dependent actin polymerization, and provides complementary but independent levels of regulation during early stages of clathrin-AP1-coated carrier biogenesis.

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  • CYFIP1 couples actin dynamics to other cellular processes, such as carrier vesicle biogenesis in the trans-Golgi network, and, via interactions with FMRP, regulates synaptic mRNA translation in an activity-dependent manner.

    “Furthermore, CYFIP1 couples actin dynamics to other cellular processes, such as carrier vesicle biogenesis in the trans-Golgi network, and, via interactions with the FRMP (Fragile X mental retardation protein), regulates synaptic mRNA translation in an activity-dependent manner.32,33”

    From The autism and schizophrenia associated gene CYFIP1 is critical for the maintenance of dendritic complexity and the stabilization of mature spines (2014) · cites this paper as [33]

    The Results (page not specified) show that CYFIP1 depletion reduces formation of TGN-derived carriers, and the Discussion describes CYFIP-containing complexes coordinating actin polymerization with carrier biogenesis. The Discussion also links CYFIP1 to FMRP, but the paper does not say that CYFIP1 regulates synaptic mRNA translation in an activity-dependent manner. (LLM, conf=0.88)

    Experimental — accuracy not yet measured
  • CYFIP1 couples local actin polymerization to membrane budding at subcellular compartments such as the trans-Golgi network.

    “CYFIP1 has been previously shown to couple local actin polymerization to membrane budding at subcellular compartments such as the trans-Golgi network.33,62”

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Authors
Anitei, M., Stange, C., Parshina, I., Baust, T., Schenck, A., Raposo, G., Kirchhausen, T., & Hoflack, B.
Affiliations
  • Biotechnologisches Zentrum (DE)
  • Harvard University (US)
  • Radboud University Nijmegen (NL)
  • Centre National de la Recherche Scientifique (FR)
Corresponding author
Hoflack, Bernard
Venue
Nature Cell Biology
Published
2010-03-14
Volume
12
Issue
4
Pages
330-340
ISSN
  • 1465-7392 (ISSN-L)
  • 1476-4679
OpenAlex
W2132552599
Cited by
102
References
5
Citations by year
2026: 1 · 2025: 3 · 2024: 2 · 2023: 4 · 2022: 6 · 2021: 3 · 2020: 2 · 2019: 3 · 2018: 7 · 2017: 2 · 2016: 8 · 2015: 7 · 2014: 16 · 2013: 10 · 2012: 9
FWCI
5.18
Type
journal article
Language
en
Update notices
erratum (2010-05-01)
Open access
Locations
  • Nature Cell Biology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • Radboud Repository (Radboud University) (submittedVersion)
Funders
  • Deutsche Forschungsgemeinschaft
  • Shandong Academy of Sciences
  • National Institutes of Health
  • National Institute of General Medical Sciences (GM075252, R01GM075252)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Caveolin-1 and cellular processes
Keywords
Arf1, Rac1, SRA, clathrin, trans-Golgi network, actin polymerization, N-WASP, Arp2/3 complex, betaPIX, membrane deformation, tubule formation, endocytic pathway
MeSH terms
Actins, Animals, Brain, Cell Fractionation, Chlorocebus aethiops, Endocytosis, HeLa Cells, Humans, Models, Biological, Swine, Time Factors, Transfection, COS Cells, Guanine Nucleotide Exchange Factors, ADP-Ribosylation Factor 1, rac1 GTP-Binding Protein, Protein Transport, trans-Golgi Network, Clathrin-Coated Vesicles, Adaptor Protein Complex 1, RNA Interference, Adaptor Proteins, Signal Transducing, Wiskott-Aldrich Syndrome Protein, Neuronal, Actin-Related Protein 2-3 Complex, Rho Guanine Nucleotide Exchange Factors

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