ArticleThe Journal of biological chemistry2016
Investigation of the Interaction between Cdc42 and Its Effector TOCA1: HANDOVER OF Cdc42 TO THE ACTIN REGULATOR N-WASP IS FACILITATED BY DIFFERENTIAL BINDING AFFINITIES.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 35 citations in OpenAlex.
- Structural basis of the protein kinase PKN1 HR1 domain oligomerization and differential regulation by RhoA and Rac1.The Journal of biological chemistry · 2026Article
- Membrane curvature initiates Cdc42-FBP17-N-WASP clustering and actin nucleation.The EMBO journal · 2026Article
- Article
- ARP2/3 regulates cell surface dynamics of CeTOCA-1 inJournal of biosciences · 2025Article
- Dataset from a human-in-the-loop approach to identify functionally important protein residues from literature.Scientific data · 2024Article
- Plasma membrane nanodeformations promote actin polymerization through CIP4/CDC42 recruitment and regulate type II IFN signaling.Science advances · 2023Article
- The role of Rho GTPase family in cochlear hair cells and hearing.Neural regeneration research · 2023Review
- Self-assembly of CIP4 drives actin-mediated asymmetric pit-closing in clathrin-mediated endocytosis.Nature communications · 2023Article
- GxcM-Fbp17/RacC-WASP signaling regulates polarized cortex assembly in migrating cells via Arp2/3.The Journal of cell biology · 2023Article
- FBP17-mediated finger-like membrane protrusions in cell competition between normal and RasV12-transformed cells.iScience · 2021Article
- Cdc42 functions as a regulatory node for tumour-derived microvesicle biogenesis.Journal of extracellular vesicles · 2021Article
- RhoGAP RGA-8 supports morphogenesis inBiology open · 2020Article
- Article
- Light-Inducible Generation of Membrane Curvature in Live Cells with Engineered BAR Domain Proteins.ACS synthetic biology · 2020Article
- BAR domain proteins-a linkage between cellular membranes, signaling pathways, and the actin cytoskeleton.Biophysical reviews · 2018Review
- Bond swapping from a charge cloud allows flexible coordination of upstream signals through WASP: Multiple regulatory roles for the WASP basic region.The Journal of biological chemistry · 2018Article
- High expression of FBP17 in invasive breast cancer cells promotes invadopodia formation.Medical oncology (Northwood, London, England) · 2018Article
- Cdc42 in actin dynamics: An ordered pathway governed by complex equilibria and directional effector handover.Small GTPases · 2017Review
- Pathogenicity-associated protein domains: The fiercely-conserved evolutionary signatures.Gene reports · 2017Review
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Transducer of Cdc42-dependent actin assembly protein 1 (TOCA1) is an effector of the Rho family small G protein Cdc42. It contains a membrane-deforming F-BAR domain as well as a Src homology 3 (SH3) domain and a G protein-binding homology region 1 (HR1) domain. TOCA1 binding to Cdc42 leads to actin rearrangements, which are thought to be involved in processes such as endocytosis, filopodia formation, and cell migration. We have solved the structure of the HR1 domain of TOCA1, providing the first structural data for this protein. We have found that the TOCA1 HR1, like the closely related CIP4 HR1, has interesting structural features that are not observed in other HR1 domains. We have also investigated the binding of the TOCA HR1 domain to Cdc42 and the potential ternary complex between Cdc42 and the G protein-binding regions of TOCA1 and a member of the Wiskott-Aldrich syndrome protein family, N-WASP. TOCA1 binds Cdc42 with micromolar affinity, in contrast to the nanomolar affinity of the N-WASP G protein-binding region for Cdc42. NMR experiments show that the Cdc42-binding domain from N-WASP is able to displace TOCA1 HR1 from Cdc42, whereas the N-WASP domain but not the TOCA1 HR1 domain inhibits actin polymerization. This suggests that TOCA1 binding to Cdc42 is an early step in the Cdc42-dependent pathways that govern actin dynamics, and the differential binding affinities of the effectors facilitate a handover from TOCA1 to N-WASP, which can then drive recruitment of the actin-modifying machinery.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.