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Eukaryotic cell migration requires continuous supply of actin polymers at the leading edges to make and extend lamellipodia or pseudopodia. Linear and branched filamentous actin polymers fuel cell migration. Branching of actin polymers in the lamellipodia/pseudopodia is facilitated by the actin-related protein (Arp) 2/3 complex, whose function is essentially controlled by the Scar/WAVE complex. In cells, the Scar/WAVE complex remains inactive, and its activation is a highly regulated and complex process. In response to signalling cues, GTP-bound Rac1 associates with Scar/WAVE and causes activation of the complex. Rac1 is essential but not sufficient for the activation of the Scar/ WAVE complex, and it requires multiple regulators, such as protein interactors and modifications (phosphorylation, ubiquitylation, etc.). Although our understanding of the regulation of the Scar/WAVE complex has improved over the last decade, it remains enigmatic. In this review, we have provided an overview of actin polymerization and discussed the importance of various regulators of Scar/WAVE activation.
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Sci Adv
May 2025
Sainsbury Laboratory (SLCU), University of Cambridge, 47 Bateman Street, Cambridge CB2 1LR, UK.
Dynamic actin cytoskeleton reorganization enables plant developmental processes requiring polarized transport such as root hair and leaf trichome formation. The SCAR/WAVE complex plays a crucial role in regulating these dynamics through ARP2/3-mediated actin branching. genes occur as small families across a wide range of plant species, but whether and how they fulfill different functions remains unclear.
View Article and Find Full Text PDFbioRxiv
March 2025
King's College London, Krause group, Randall Centre for Cell and Molecular Biophysics, New Hunt's House, Guy's Campus, London, SE1 1UL, UK.
Cell migration is crucial for development and deregulation causes diseases. The Scar/WAVE complex promotes mesenchymal cell migration through Arp2/3 mediated lamellipodia protrusion. We previously discovered that all isoforms of Nance-Horan Syndrome-like 1 (NHSL1) protein interact directly with the Scar/WAVE complex and the NHSL1-F1 isoform negatively regulates Scar/WAVE-Arp2/3 activity thereby inhibiting 2D random cell migration.
View Article and Find Full Text PDFCommun Biol
February 2025
Laboratoire d'Optique et Biosciences (LOB), CNRS, INSERM, Ecole Polytechnique, Institut Polytechnique de Paris, 91120, Palaiseau, France.
Cell migrations are crucial for embryonic development, wound healing, the immune response, as well as for cancer progression. During mesenchymal cell migration, the Rac1-WAVE-Arp2/3 signalling pathway induces branched actin polymerisation, which protrudes the membrane and allows migration. Fine-tuning the activity of the Rac1-WAVE-Arp2/3 pathway modulates protrusion lifetime and migration persistence.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
February 2025
National Key Laboratory for Germplasm Innovation and Utilization of Horticultural Crops, College of Horticulture and Forestry Sciences, Huazhong Agricultural University, Wuhan 430070, China.
Plant cytokinesis requires coordination between the actin cytoskeleton, microtubules, and membranes to guide division plane formation and cell plate expansion; how these regulatory factors are coordinated remains unknown. The actin cytoskeleton assembly is controlled by several actin nucleation factors, such as the SCAR/WAVE complex, which regulates actin nucleation and branching through the activation of the ARP2/3 complex. The activity of these actin regulatory proteins is likely influenced by interactions with specific membranes; however, the molecular basis and the biological relevance of SCAR-membrane interactions are also unclear.
View Article and Find Full Text PDFStress Biol
November 2024
State Key Laboratory of Crop Stress Resistance and High-Efficiency Production and College of Life Sciences, Northwest A&F University, 22 Xinong Rd, Yangling, Shaanxi, 712100, China.
Developmental plasticity is critical for plants to adapt to constantly changing environments. Plant root hairs display dramatic plasticity under different environments and therefore play crucial roles in defense against environmental stressors. Here, we report the isolation of an Arabidopsis mutant, salinity over-sensitive mutant 1-1 (som1-1), also exhibiting root hair developmental defects.
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