Cited by 385Axon Guidance and Neuronal SignalingProtein Kinase Regulation and GTPase SignalingNeurogenesis and neuroplasticity mechanisms

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The sequential activity of the GTPases Rap1B and Cdc42 determines neuronal polarity.

Schwamborn, Jens C, Püschel, Andreas W·2004·Nature Neuroscience

DOI 10.1038/nn1295

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Abstract

The establishment of a polarized morphology is an essential step in the differentiation of neurons with a single axon and multiple dendrites. In cultured rat hippocampal neurons, one of several initially indistinguishable neurites is selected to become the axon. Both phosphatidylinositol 3,4,5-trisphosphate and the evolutionarily conserved Par complex (comprising Par3, Par6 and an atypical PKC (aPKC) such as PKClambda or PKCzeta) are involved in axon specification. However, the initial signals that establish cellular asymmetry and the pathways that subsequently translate it into structural changes remain to be elucidated. Here we show that localization of the GTPase Rap1B to the tip of a single neurite is a decisive step in determining which neurite becomes the axon. Using GTPase mutants and RNA interference, we found that Rap1B is necessary and sufficient to initiate the development of axons upstream of Cdc42 and the Par complex.

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Authors: Schwamborn, J. C., & Püschel, A. W.
Affiliations: University of Münster (DE)
Corresponding author: Püschel, Andreas W
ORCID: Schwamborn, Jens C
Püschel, Andreas W
Venue: Nature Neuroscience
Publisher: Springer Science and Business Media LLC
Published: 2004-08-01
Volume: 7
Issue: 9
Pages: 923-929
ISSN: 1097-6256 (ISSN-L)
1546-1726
DOI: 10.1038/nn1295
OpenAlex: W2059346427
Cited by: 385
References: 39
Citations by year: 2026: 1 · 2025: 3 · 2024: 5 · 2023: 5 · 2022: 15 · 2021: 8 · 2020: 8 · 2019: 10 · 2018: 15 · 2017: 18 · 2016: 18 · 2015: 16 · 2014: 13 · 2013: 20 · 2012: 28
FWCI: 11.00
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature Neuroscience (publishedVersion)
PubMed (publishedVersion)
Open Repository and Bibliography (University of Luxembourg) (submittedVersion)
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 › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Keywords: Rap1b, Cdc42, neuronal polarity, axon specification, GTPase, Par complex, phosphatidylinositol 3,4,5-trisphosphate, atypical PKC, hippocampal neurons, neuronal differentiation
MeSH terms: Animals, Animals, Newborn, Antibodies, Monoclonal, Axons, Carrier Proteins, Cells, Cultured, Dendrites, Embryo, Mammalian, Hippocampus, Immunohistochemistry, Luminescent Proteins, Microtubule-Associated Proteins, Nerve Tissue Proteins, Neurons, Phalloidine, Protein Kinase C, Proto-Oncogene Proteins, RNA, Messenger, Time Factors, Transfection, Cytochalasin D, Protein Serine-Threonine Kinases, Gene Transfer Techniques, Body Patterning, Reverse Transcriptase Polymerase Chain Reaction, GTP Phosphohydrolases, rap GTP-Binding Proteins, rhoA GTP-Binding Protein, cdc42 GTP-Binding Protein, RNA Interference, Green Fluorescent Proteins, Proto-Oncogene Proteins c-akt, Mice, Rats

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The sequential activity of the GTPases Rap1B and Cdc42 determines neuronal polarity.

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