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<p>Polymerization of branched actin networks by the ARP2/3 complex plays a critical role in diverse cellular processes. ARP2/3 activity is tightly controlled by the upstream CDC-42 GTPase and effectors such as the Wiscott–Aldrich syndrome protein (N-WASP/Wiscott-Aldrich Syndrome Protein (WSP-1)) and members of the F-BAR containing transducer of CDC-42-dependent actin assembly (TOCA) protein family. While the mechanisms governing WASP/N-WASP (neural-WASP) functioning are well understood, the regulatory dynamics of TOCA proteins at the cell cortex remain poorly characterized. Here, using the <i>Caenorhabditis elegans</i> zygote as a model system, we investigated the role of cortical F-actin structures – both branched and linear – in modulating surface dynamics of CeTOCA-1, the nematode ortholog of mammalian TOCA-1. In our <i>in silico</i> analysis, iPTM values associated with the interaction between different domains of CeTOCA-1 and CDC-42 suggested that while the HR-1 domain is essential for this interaction, the SH3 domain is dispensable for complex formation between the two proteins. Further, we experimentally disrupted ARP2/3 and CYK-1/formin-polymerized F-actin structures in <i>C. elegans</i> zygotes to examine the role of cortical F-actin on CeTOCA-1 assembly dynamics and biophysical properties. Co-localization studies revealed a preferential association between CeTOCA-1 and the pool of F-actin structures polymerized by ARP2/3. Disruption of ARP2/3 led to the formation of larger CeTOCA-1 clusters, prolonged cluster lifetime on the cell surface, and reduced cluster mobility. These findings suggest that distinct F-actin structures play specialized roles in mediating plasma membrane interactions and regulating surface dynamics of CeTOCA-1 clusters.</p>

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ARP2/3 regulates cell surface dynamics of CeTOCA-1 in C. elegans zygotes

  • 期刊论文

  • 发表日期：

    2025年5月15日

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  • Aadya Nageswaran,
  • Promiti Mitra,
  • Megha Rai,
  • Diya Anand,
  • Yogesh Pratap,
  • Anup Padmanabhan

摘要

Polymerization of branched actin networks by the ARP2/3 complex plays a critical role in diverse cellular processes. ARP2/3 activity is tightly controlled by the upstream CDC-42 GTPase and effectors such as the Wiscott–Aldrich syndrome protein (N-WASP/Wiscott-Aldrich Syndrome Protein (WSP-1)) and members of the F-BAR containing transducer of CDC-42-dependent actin assembly (TOCA) protein family. While the mechanisms governing WASP/N-WASP (neural-WASP) functioning are well understood, the regulatory dynamics of TOCA proteins at the cell cortex remain poorly characterized. Here, using the Caenorhabditis elegans zygote as a model system, we investigated the role of cortical F-actin structures – both branched and linear – in modulating surface dynamics of CeTOCA-1, the nematode ortholog of mammalian TOCA-1. In our in silico analysis, iPTM values associated with the interaction between different domains of CeTOCA-1 and CDC-42 suggested that while the HR-1 domain is essential for this interaction, the SH3 domain is dispensable for complex formation between the two proteins. Further, we experimentally disrupted ARP2/3 and CYK-1/formin-polymerized F-actin structures in C. elegans zygotes to examine the role of cortical F-actin on CeTOCA-1 assembly dynamics and biophysical properties. Co-localization studies revealed a preferential association between CeTOCA-1 and the pool of F-actin structures polymerized by ARP2/3. Disruption of ARP2/3 led to the formation of larger CeTOCA-1 clusters, prolonged cluster lifetime on the cell surface, and reduced cluster mobility. These findings suggest that distinct F-actin structures play specialized roles in mediating plasma membrane interactions and regulating surface dynamics of CeTOCA-1 clusters.