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Cited by 391Protein Kinase Regulation and GTPase SignalingAxon Guidance and Neuronal SignalingNeuroscience and Neuropharmacology Research

Rho family GTPases: Key players in neuronal development, neuronal survival, and neurodegeneration

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Stankiewicz, Trisha R., Linseman, Daniel A.·2014·Frontiers in Cellular Neuroscience
DOI 10.3389/fncel.2014.00314PMC PMC4187614
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Abstract

The Rho family of GTPases belongs to the Ras superfamily of low molecular weight (∼21 kDa) guanine nucleotide binding proteins. The most extensively studied members are RhoA, Rac1, and Cdc42. In the last few decades, studies have demonstrated that Rho family GTPases are important regulatory molecules that link surface receptors to the organization of the actin and microtubule cytoskeletons. Indeed, Rho GTPases mediate many diverse critical cellular processes, such as gene transcription, cell-cell adhesion, and cell cycle progression. However, Rho GTPases also play an essential role in regulating neuronal morphology. In particular, Rho GTPases regulate dendritic arborization, spine morphogenesis, growth cone development, and axon guidance. In addition, more recent efforts have underscored an important function for Rho GTPases in regulating neuronal survival and death. Interestingly, Rho GTPases can exert either a pro-survival or pro-death signal in neurons depending upon both the cell type and neurotoxic insult involved. This review summarizes key findings delineating the involvement of Rho GTPases and their effectors in the regulation of neuronal survival and death. Collectively, these results suggest that dysregulation of Rho family GTPases may potentially underscore the etiology of some forms of neurodegenerative disease such as amyotrophic lateral sclerosis.

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  • Many neuronal studies support the general model that Rac and Cdc42 stimulate neuronal growth cone dynamics, dendritic spine formation, and axonal extension and guidance, while RhoA inhibits these processes and causes axonal and dendritic retraction and spine and synapse loss.

    “Many neuronal studies support the general model that Rac and Cdc42 stimulate these processes, while RhoA inhibits them and causes axonal and dendritic retraction and spine and synapse loss.”

    From RhoA Signaling in Neurodegenerative Diseases (2022) · cites this paper as [1]

    Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

    Experimental — accuracy not yet measured

  • RhoA and many of its downstream effector proteins are highly expressed in the nervous system, implying an important role for RhoA signaling in neurons and glial cells.

    “RhoA and many of its downstream effector proteins are highly expressed in the nervous system, implying an important role for RhoA signaling in neurons and glial cells.”

    From RhoA Signaling in Neurodegenerative Diseases (2022) · cites this paper as [1]

    The “Rho in Neuronal Development” section (page unavailable) describes roles for RhoA in neurons and radial glia, supporting the inference that its signaling matters in both. Neither that section nor the passages retrieved on expression state that RhoA and many downstream effectors are highly expressed throughout the nervous system; the expression findings concern specific injury conditions. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • RhoA can induce apoptosis via direct activation of MAPK p38 and JNK signaling pathways, which induce apoptosis through activation of proapoptotic Bcl-2 family members Bad and Bax.

    “Furthermore, RhoA can induce apoptosis via direct activation of the mitogen-activated protein kinases (MAPK) p38 and c-Jun N-terminal kinase (JNK) signaling pathways, which induce apoptosis through activation of proapoptotic Bcl-2 family members, e.g., Bad and Bax [1] (Figure 3).”

    From RhoA Signaling in Neurodegenerative Diseases (2022) · cites this paper as [1]

    The Figure 2 caption in the section on antagonistic Rac and Rho signaling says Rho can provoke apoptosis through p38- or JNK-dependent pathways that activate pro-apoptotic Bcl-2 family proteins. The copy does not say RhoA directly activates those kinases or identify Bad and Bax as the proteins activated by those pathways; it names Bad and Bax in connection with their inhibition by Rac/Akt. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • RhoA and Rac/Cdc42 typically exhibit an antagonistic relationship to regulate neuronal morphology.

    “Hence, RhoA and Rac/Cdc42 typically exhibit an antagonistic relationship to regulate neuronal morphology [1,7].”

    From RhoA Signaling in Neurodegenerative Diseases (2022) · cites this paper as [1]

  • Rac typically promotes neuronal survival, while RhoA induces neuronal apoptosis.

    “Similar to their opposing effects on cytoskeletal dynamics, Rac typically promotes neuronal survival, while RhoA induces neuronal apoptosis [1].”

    From RhoA Signaling in Neurodegenerative Diseases (2022) · cites this paper as [1]

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Cited by

Sorted by citations

Authors
Stankiewicz, T. R., & Linseman, D. A.
Affiliations
University of Denver (US)
Corresponding author
Linseman, Daniel A.
ORCID
Linseman, Daniel A.
Venue
Frontiers in Cellular Neuroscience
Publisher
Frontiers Media SA
Published
2014-10-07
Volume
8
Pages
314-314
ISSN
1662-5102 (ISSN-L)
DOI
10.3389/fncel.2014.00314
PMC
PMC4187614
OpenAlex
W2076316109
Cited by
391
References
0
Citations by year
2026: 26 · 2025: 34 · 2024: 36 · 2023: 45 · 2022: 32 · 2021: 34 · 2020: 36 · 2019: 32 · 2018: 33 · 2017: 29 · 2016: 35 · 2015: 18
FWCI
2.59
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Frontiers in Cellular Neuroscience (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • 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
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
Rho GTPases, RhoA, Rac1, Cdc42, neuronal development, neuronal survival, neuronal cell death, neurodegeneration, actin cytoskeleton, microtubule cytoskeleton, dendritic branching, dendritic spine morphogenesis, axon guidance, neurotoxicity, amyotrophic lateral sclerosis, Ras superfamily

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