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Cited by 131Neuroscience and Neuropharmacology ResearchGenetics and Neurodevelopmental DisordersAxon Guidance and Neuronal Signaling

Chemical genetic identification of NDR1/2 kinase substrates AAK1 and Rabin8 Uncovers their roles in dendrite arborization and spine development.

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Ultanir, Sila K., Hertz, Nicholas T., Li, Guangnan, Ge, Woo-Ping, Burlingame, Alma L., Pleasure, Samuel J., Shokat, Kevan M., Jan, Lily Yeh +1 more·2012·Neuron
DOI 10.1016/j.neuron.2012.01.019PMC PMC3333840
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Abstract

Dendrite arborization and synapse formation are essential for wiring the neural circuitry. The evolutionarily conserved NDR1/2 kinase pathway, important for polarized growth from yeast to mammals, controls dendrite growth and morphology in the worm and fly. The function of NDR1/2 in mammalian neurons and their downstream effectors were not known. Here we show that the expression of dominant negative (kinase-dead) NDR1/2 mutants or siRNA increase dendrite length and proximal branching of mammalian pyramidal neurons in cultures and in vivo, whereas the expression of constitutively active NDR1/2 has the opposite effect. Moreover, NDR1/2 contributes to dendritic spine development and excitatory synaptic function. We further employed chemical genetics and identified NDR1/2 substrates in the brain, including two proteins involved in intracellular vesicle trafficking: AAK1 (AP-2 associated kinase) and Rabin8, a GDP/GTP exchange factor (GEF) of Rab8 GTPase. We finally show that AAK1 contributes to dendrite growth regulation, and Rabin8 regulates spine development.

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  • Mammalian Ndr kinases have been implicated in the regulation of centrosome duplication and in dendrite arborization and spine formation during neuronal development.

    “Mammalian Ndr kinases have been implicated in the regulation of centrosome duplication and in dendrite arborization and spine formation during neuronal development (Hergovich et al., 2007; Ultanir et al., 2012).”

    From Rassf5 and Ndr kinases act in a novel pathway regulating neuronal polarity through Par3 phosphorylation (2014) · cites this paper as Ultanir et al., 2012

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Authors
Ultanir, S. K., Hertz, N. T., Li, G., Ge, W.-P., Burlingame, A. L., Pleasure, S. J., Shokat, K. M., Jan, L. Y., & Jan, Y.-N.
Affiliations
  • Howard Hughes Medical Institute (US)
  • University of California, San Francisco (US)
Corresponding author
  • Ultanir, Sila K.
  • Jan, Yuh-Nung
ORCID
Venue
Neuron
Publisher
Elsevier BV
Published
2012-03
Volume
73
Issue
6
Pages
1127-1142
ISSN
0896-6273 (ISSN-L)
DOI
10.1016/j.neuron.2012.01.019
PMC
PMC3333840
OpenAlex
W2101090931
Cited by
131
References
3
Citations by year
2026: 5 · 2025: 5 · 2024: 5 · 2023: 12 · 2022: 4 · 2021: 5 · 2020: 6 · 2019: 9 · 2018: 15 · 2017: 8 · 2016: 13 · 2015: 13 · 2014: 14 · 2013: 14 · 2012: 3
FWCI
5.80
Type
journal article
Language
en
Open access
Licence
Locations
  • Neuron (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Howard Hughes Medical Institute
  • National Institutes of Health (5r01eb001987-15)
  • National Institute of Mental Health (R01MH066084, R01MH084234, R01MH077694)
  • National Institute of General Medical Sciences (P41GM103481)
  • National Institute of Neurological Disorders and Stroke (R37NS040929)
  • National Institute of Biomedical Imaging and Bioengineering (R01-EB001987)
  • National Center for Research Resources (RR015804, RR 001614, P41RR001614, S10RR015804)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
Keywords
dendritic branching, dendritic spine development, AAK1, kinase substrates, chemical genetics, pyramidal neurons, excitatory synapses, vesicle trafficking, polarized growth
MeSH terms
N-myc Downstream-Regulated Gene 1 Protein, Age Factors, Animals, Animals, Newborn, Autoantigens, Cells, Cultured, Dendrites, Embryo, Mammalian, Hippocampus, Humans, Membrane Proteins, Microtubule-Associated Proteins, Models, Biological, Models, Molecular, Mutation, Neurons, Phosphorylation, Synapses, Transfection, Protein Serine-Threonine Kinases, Electroporation, Patch-Clamp Techniques, Gene Expression Regulation, Developmental, Excitatory Postsynaptic Potentials, Rats, Long-Evans, Guanine Nucleotide Exchange Factors, RNA, Small Interfering, Dendritic Spines, Green Fluorescent Proteins, Mice, Rats

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