DOCK9 induces membrane ruffles and Rac1 activity in cancer HeLa epithelial cells
Open accessAbstract
Dedicator-of-cytokinesis (DOCK) proteins are a family of guanine-nucleotide exchange factors (GEF) for Rho GTPases. The DOCK-D homology subfamily comprises DOCK9, DOCK10, and DOCK11. DOCK9 and DOCK11 are GEFs for Cdc42 and induce filopodia, while DOCK10 is a dual GEF for Cdc42 and Rac1 and induces filopodia and ruffles. We provide data showing that DOCK9, the only one of the DOCK-D members that is not considered hematopoietic, is nevertheless expressed at high levels in T lymphocytes, as do DOCK10 and DOCK11, although unlike these, it is not expressed in B lymphocytes. To investigate DOCK9 function, we have created a stable HeLa clone with inducible expression of HA-DOCK9. Induction of expression of HA-DOCK9 produced loss of elongation and polygonal shape of HeLa cells. Regarding membrane protrusions, HA-DOCK9 prominently induced filopodia, but also an increase of membrane ruffles. The latter was consistent with an increase in the levels of activation of Rac1, suggesting that DOCK9 carries a secondary ability to induce ruffles through activation of Rac1.
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Overexpression of DOCK9 coincides with an increase in RAC1 activity.
“Although not reported as a substrate, overexpression of DOCK9 coincided with an increase in RAC1 activity.”
From RHO to the DOCK for GDP disembarking: Structural insights into the DOCK GTPase nucleotide exchange factors (2021) · cites this paper as [122]
In HeLa epithelial cells, DOCK9 expression reduced elongated cell morphology and led to increased filopodia and membrane ruffling.
“The role of DOCK9 in structural remodeling of cells was investigated in HeLa epithelial cells, where its expression reduced elongated cell morphology and led to increased filopodia and membrane ruffling (122).”
From RHO to the DOCK for GDP disembarking: Structural insights into the DOCK GTPase nucleotide exchange factors (2021) · cites this paper as [122]
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Zizimin1, a novel Cdc42 activator, reveals a new GEF domain for Rho proteins
Meller, N., Irani-Tehrani, M., Kiosses, W. B., Del Pozo, M. A., & Schwartz, M. A. (2002) · Nature Cell Biology · doi:10.1038/ncb835 · Cited by 171 · see citing works
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Thompson, A. P., Bitsina, C., Gray, J. L., von Delft, F., & Brennan, P. E. (2021) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2021.100521 · Cited by 21 · see citing works
“The role of DOCK9 in structural remodeling of cells was investigated in HeLa epithelial cells, where its expression reduced elongated cell morphology and led to increased filopodia and membrane ruffling (122).”
Background
- Authors
- Ruiz-Lafuente, N., Minguela, A., & Parrado, A.
- Affiliations
- Instituto Murciano de Investigación Biosanitaria (ES)
- Corresponding author
- Parrado, Antonio
- Venue
- Biochemistry and Biophysics Reports
- Publisher
- Elsevier BV
- Published
- 2018-07
- Volume
- 14
- Pages
- 178-181
- ISSN
- 2405-5808 (ISSN-L)
- PMC
- PMC5986721
- OpenAlex
- W2804800131
- Cited by
- 11
- References
- 1
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 1 · 2021: 5 · 2020: 1 · 2019: 1
- FWCI
- 0.62
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Biochemistry and Biophysics Reports (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Fundación Séneca (08721/PI/08)
- Instituto de Salud Carlos III
- 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, Rho GTPases, Rac1 activation, ruffles, filopodia, cell shape, HeLa cells, T cells, B cells, Cdc42
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