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Cited by 112Axon Guidance and Neuronal SignalingProtein Kinase Regulation and GTPase SignalingCellular transport and secretion

Ral GTPases regulate neurite branching through GAP-43 and the exocyst complex

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Lalli, Giovanna, Hall, Alan·2005·The Journal of Cell Biology
DOI 10.1083/jcb.200507061PMC PMC2171284
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Abstract

Neurite branching is essential for the establishment of appropriate neuronal connections during development and regeneration. We identify the small GTPase Ral as a mediator of neurite branching. Active Ral promotes neurite branching in cortical and sympathetic neurons, whereas Ral inhibition decreases laminin-induced branching. In addition, depletion of endogenous Ral by RNA interference decreases branching in cortical neurons. The two Ral isoforms, RalA and -B, promote branching through distinct pathways, involving the exocyst complex and phospholipase D, respectively. Finally, Ral-dependent branching is mediated by protein kinase C–dependent phosphorylation of 43-kD growth-associated protein, a crucial molecule involved in pathfinding, plasticity, and regeneration. These findings highlight an important role for Ral in the regulation of neuronal morphology.

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Crossref · 10.1083/jcb.200507061

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  • Remodelling neuronal connections by synaptic activity requires membrane trafficking.

    “Remodelling neuronal connections by synaptic activity requires membrane trafficking.”

    From Ral mediates activity‐dependent growth of postsynaptic membranes via recruitment of the exocyst (2013) · cites this paper as Lalli and Hall, 2005

    The Introduction says neurite branching likely involves membrane delivery, and the Discussion proposes membrane delivery as part of a mechanism promoting branching. Neither passage establishes that remodelling driven by synaptic activity requires membrane trafficking; the paper discusses developmental branching and other cues instead. Page numbers are not available in our copy. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • Membrane addition is critical for permitting neurite outgrowth and branching.

    “Membrane addition is critical for permitting neurite outgrowth and branching (Steiner et al, 2002;Lalli and Hall, 2005)”

    From Ral mediates activity‐dependent growth of postsynaptic membranes via recruitment of the exocyst (2013) · cites this paper as Lalli and Hall, 2005

    The Introduction says neurite branching likely requires membrane delivery, and the Discussion proposes that exocyst-mediated membrane delivery could promote branching. The paper also reports that disrupting exocyst components prevents neurite extension, but it does not establish that membrane addition itself is critical for both outgrowth and branching; its branching mechanism is presented as a possibility. Our copy provides section labels but no page numbers. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

  • RalA and the exocyst are known to regulate early stages of neuronal development, including neurite formation.

    “RalA and the exocyst are known to regulate early stages of neuronal development, including neurite formation (Lalli and Hall, 2005).”

    From Ral mediates activity‐dependent growth of postsynaptic membranes via recruitment of the exocyst (2013) · cites this paper as Lalli and Hall, 2005

    The Abstract reports that RalA promotes neurite branching through the exocyst complex, supporting a role in neuronal development. But the Discussion distinguishes branching from neurite formation: neurites still grow when Ral is inhibited, and the authors say Ral is not necessary for neurite extension per se. The claim's reference to neurite formation therefore goes beyond this paper's finding about RalA. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • While RalA activity promotes the outgrowth and branching of neurites in newly dissociated neurons in a Sec5-dependent manner, at later stages, it may regulate aspects of dendritic spine dynamics.

    “While RalA activity promotes the outgrowth and branching of neurites in newly dissociated neurons in a Sec5-dependent manner (Lalli and Hall, 2005), at later stages, it may regulate aspects of dendritic spine dynamics.”

    From Ral mediates activity‐dependent growth of postsynaptic membranes via recruitment of the exocyst (2013) · cites this paper as Lalli and Hall, 2005

    The Results (‘Active Ral increases neurite branching’; ‘RalA and -B regulate branching through different effectors’, page unavailable) show that active RalA increases branching in recently plated neurons and that preventing its interaction with the Sec5-containing exocyst impairs this effect. They also report increased axon length with active RalA, but do not establish that this outgrowth effect is Sec5-dependent. The later-stage dendritic-spine suggestion follows the citation and is not attributed to this paper. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Ral, via the exocyst, promotes neurite branching and participates in establishing neuronal polarity.

    “Ral, via the exocyst, promotes neurite branching and participates in establishing neuronal polarity”

    From Ral mediates activity‐dependent growth of postsynaptic membranes via recruitment of the exocyst (2013) · cites this paper as Lalli and Hall, 2005

    The Introduction and Discussion support the claim that RalA promotes neurite branching through the exocyst complex. But the Discussion says Ral activity is dispensable for establishing neuronal polarity, contrary to the claim’s second part. Page numbers were not provided in our copy. (LLM, conf=0.90)

    Experimental — accuracy not yet measured

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Cites

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Cited by

Sorted by citations

Authors
Lalli, G., & Hall, A.
Affiliations
MRC Laboratory for Molecular Cell Biology (GB)
Corresponding author
Hall, Alan
ORCID
Lalli, Giovanna
Venue
The Journal of Cell Biology
Publisher
Rockefeller University Press
Published
2005-12-05
Volume
171
Issue
5
Pages
857-869
ISSN
  • 0021-9525 (ISSN-L)
  • 1540-8140
DOI
10.1083/jcb.200507061
PMC
PMC2171284
OpenAlex
W2132206752
Cited by
112
References
1
Citations by year
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FWCI
1.82
Type
journal article
Language
en
Open access
Licence
cc-by-nc-sa
Locations
  • The Journal of Cell Biology (publishedVersion)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
  • Research Portal (King's College London) (submittedVersion)
Funders
Wellcome Trust
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
  • 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 transport and secretion
Keywords
Ral GTPase, neurite branching, GAP-43, exocyst complex, phospholipase D, protein kinase C, neuronal morphology, cortical neurons, sympathetic neurons, laminin, neuronal regeneration, neuronal development
MeSH terms
Actins, Animals, Cells, Cultured, Chlorocebus aethiops, Cerebral Cortex, Laminin, Membrane Proteins, Neurons, Phospholipase D, Phosphorylation, Protein Kinase C, Signal Transduction, Neurites, Rats, Sprague-Dawley, Superior Cervical Ganglion, GAP-43 Protein, ral GTP-Binding Proteins, RNA, Small Interfering, Rats

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