Dock GEFs and their therapeutic potential: Neuroprotection and axon regeneration
Abstract
The dedicator of cytokinesis (Dock) family is composed of atypical guanine exchange factors (GEFs) that activate the Rho GTPases Rac1 and Cdc42. Rho GTPases are best documented for their roles in actin polymerization and they regulate important cellular functions, including morphogenesis, migration, neuronal development, and cell division and adhesion. To date, 11 Dock family members have been identified and their roles have been reported in diverse contexts. There has been increasing interest in elucidating the roles of Dock proteins in recent years and studies have revealed that they are potential therapeutic targets for various diseases, including glaucoma, Alzheimer's disease, cancer, attention deficit hyperactivity disorder and combined immunodeficiency. Among the Dock proteins, Dock3 is predominantly expressed in the central nervous system and recent studies have revealed that Dock3 plays a role in protecting retinal ganglion cells from neurotoxicity and oxidative stress as well as in promoting optic nerve regeneration. In this review, we discuss the current understanding of the 11 Dock GEFs and their therapeutic potential, with a particular focus on Dock3 as a novel target for the treatment of glaucoma and other neurodegenerative diseases.
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DOCK1 has reported roles in cell migration, invasion, and phagocytosis.
“It has reported roles in cell migration, invasion, and phagocytosis (48, 51, 52, 53, 54).”
From RHO to the DOCK for GDP disembarking: Structural insights into the DOCK GTPase nucleotide exchange factors (2021) · cites this paper as [48]
DOCK7 is highly expressed in the brain.
“It is highly expressed in the brain, where it has roles in axon formation, polarity, and myelination (42, 48, 104, 105).”
From RHO to the DOCK for GDP disembarking: Structural insights into the DOCK GTPase nucleotide exchange factors (2021) · cites this paper as [48]
DOCK7 has roles in axon formation, polarity, and myelination.
“It is highly expressed in the brain, where it has roles in axon formation, polarity, and myelination (42, 48, 104, 105).”
From RHO to the DOCK for GDP disembarking: Structural insights into the DOCK GTPase nucleotide exchange factors (2021) · cites this paper as [48]
The DOCK-D subfamily has roles in the immune system and neurology.
“The DOCK-D subfamily, although not as well studied as other DOCKs, has been shown to have roles in the immune system and neurology (36, 48, 120).”
From RHO to the DOCK for GDP disembarking: Structural insights into the DOCK GTPase nucleotide exchange factors (2021) · cites this paper as [48]
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“DOCK family functions in specific areas such as neurology (36, 48), immunology (49, 50), and cancer (17) have been extensively reviewed, and what follows is a summary of DOCK function with a focus on disease association of each family member (Table 2).”
Background
- Authors
- Namekata, K., Kimura, A., Kawamura, K., Harada, C., & Harada, T.
- Affiliations
- Tokyo Metropolitan Institute of Medical Science (JP)
- Corresponding author
- Harada, Takayuki
- Venue
- Progress in Retinal and Eye Research
- Publisher
- Elsevier BV
- Published
- 2014-11
- Volume
- 43
- Pages
- 1-16
- ISSN
- 1350-9462 (ISSN-L)
- OpenAlex
- W2020921152
- Cited by
- 57
- References
- 12
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 4 · 2023: 3 · 2022: 4 · 2021: 7 · 2020: 4 · 2019: 5 · 2018: 5 · 2017: 4 · 2016: 3 · 2015: 11 · 2014: 4
- FWCI
- 1.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Progress in Retinal and Eye Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology
- Topics
- Health Sciences › Medicine › Ophthalmology › Glaucoma and retinal disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
- Keywords
- guanine nucleotide exchange factor, Rho GTPases, Rac1, Cdc42, neuroprotection, axon regeneration, optic nerve regeneration, retinal ganglion cells, glaucoma, neurodegenerative diseases, therapeutic target, actin polymerization
- MeSH terms
- Animals, Axons, Disease Models, Animal, Glaucoma, Humans, Nerve Regeneration, Retinal Ganglion Cells, Neuroprotective Agents, Neurodegenerative Diseases, Guanine Nucleotide Exchange Factors, Mice
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