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Cited by 37Protein Kinase Regulation and GTPase SignalingCellular Mechanics and InteractionsCellular transport and secretion

Dock10, a Cdc42 and Rac1 GEF, induces loss of elongation, filopodia, and ruffles in cervical cancer epithelial HeLa cells

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Ruiz-Lafuente, Natalia, Alcaraz-García, María-José, García-Serna, Azahara-María, Sebastián-Ruiz, Silvia, Moya-Quiles, María-Rosa, García-Alonso, Ana-María, Parrado, Antonio·2015·Biology Open
DOI 10.1242/bio.20149050PMC PMC4434814
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Abstract

Dock10 is one of the three members of the Dock-D family of Dock proteins, a class of guanine nucleotide exchange factors (GEFs) for Rho GTPases. Its homologs Dock9 and Dock11 are Cdc42 GEFs. Dock10 is required for maintenance of rounded morphology and amoeboid-type movement. Full-length isoforms of Dock10 have been recently cloned. Here, we address GTPase specificity and GEF activity of Dock10. In order of decreasing intensity, Dock10 interacted with nucleotide-free Rac1, Cdc42, and Rac3, and more weakly with Rac2, RhoF, and RhoG. Inducible expression of Dock10 in HeLa epithelial cells promoted GEF activity on Cdc42 and Rac1, and a morphologic change in two-dimensional culture consisting in loss of cell elongation, increase of filopodia, and ruffles. Area in contact with the substrate of cells that spread with non-elongated morphology was larger in cells expressing Dock10. Inducible expression of constitutively active mutants of Cdc42 and Rac1 in HeLa cells also induced loss of elongation. However, Cdc42 induced filopodia and contraction, and Rac1 induced membrane ruffles and flattening. When co-expressed with Dock10, Cdc42 potentiated filopodia, and Rac1 potentiated ruffles. These results suggest that Dock10 functions as a dual GEF for Cdc42 and Rac1, affecting cell morphology, spreading and actin cytoskeleton protrusions of adherent HeLa cells.

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  • DOCK10 appears to bind more than one GTPase, as evidenced by recent crystal structures in complex with CDC42 and RAC3.

    “DOCK10 also appears to bind more than one GTPase as evidenced by recent crystal structures in complex with CDC42 and RAC3 (Table 1) (42, 43, 44).”

    From RHO to the DOCK for GDP disembarking: Structural insights into the DOCK GTPase nucleotide exchange factors (2021) · cites this paper as [44]

    The Results section, “Interaction of Dock10 with Rho GTPases” (page not provided), reports that both Dock10 isoforms interacted with Cdc42 and Rac3. It describes in vitro interaction assays, not crystal structures of Dock10 in complex with those GTPases, so the stated structural evidence is unsupported by this source. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • DOCK10 is a GEF for both CDC42 and RAC GTPases.

    “DOCK10 is a GEF for both CDC42 and RAC GTPases (42, 43, 44).”

    From RHO to the DOCK for GDP disembarking: Structural insights into the DOCK GTPase nucleotide exchange factors (2021) · cites this paper as [44]

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Authors
Ruiz-Lafuente, N., Alcaraz-García, M.-J., García-Serna, A.-M., Sebastián-Ruiz, S., Moya-Quiles, M.-R., García-Alonso, A.-M., & Parrado, A.
Affiliations
  • Instituto Murciano de Investigación Biosanitaria (ES)
  • Immunology Service, Virgen de la Arrixaca Clinic University Hospital, Institute for Biohealth Research (IMIB-Arrixaca), Ctra. Madrid-Cartagena s/n, El Palmar, 30120, Murcia, Spain
Corresponding author
Parrado, Antonio
ORCID
Parrado, Antonio
Venue
Biology Open
Publisher
The Company of Biologists
Published
2015-05-15
Volume
4
Issue
5
Pages
627-635
ISSN
2046-6390 (ISSN-L)
DOI
10.1242/bio.20149050
PMC
PMC4434814
OpenAlex
W2145562832
Cited by
37
References
3
Citations by year
2025: 1 · 2024: 1 · 2023: 2 · 2022: 6 · 2021: 7 · 2020: 5 · 2019: 2 · 2018: 4 · 2017: 3 · 2016: 4 · 2015: 2
FWCI
1.88
Type
journal article
Language
en
Open access
Licence
Locations
  • Biology Open (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
Keywords
guanine nucleotide exchange factor, Cdc42, Rac1, RAC3, Rho GTPases, cell morphology, cell spreading, filopodia, ruffles, actin cytoskeleton, HeLa cells, cervical cancer

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