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Cited by 75Neuroscience and Neuropharmacology ResearchGenetics and Neurodevelopmental DisordersAxon Guidance and Neuronal Signaling

MST3 Kinase Phosphorylates TAO1/2 to Enable Myosin Va Function in Promoting Spine Synapse Development

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Ultanir, Sila K., Yadav, Smita, Hertz, Nicholas T., Oses-Prieto, Juan A., Claxton, Suzanne, Burlingame, Alma L., Shokat, Kevan M., Jan, Lily Y. +1 more·2014·Neuron
DOI 10.1016/j.neuron.2014.10.025PMC PMC4407996
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Abstract

Mammalian Sterile 20 (Ste20)-like kinase 3 (MST3) is a ubiquitously expressed kinase capable of enhancing axon outgrowth. Whether and how MST3 kinase signaling might regulate development of dendritic filopodia and spine synapses is unknown. Through shRNA-mediated depletion of MST3 and kinase-dead MST3 expression in developing hippocampal cultures, we found that MST3 is necessary for proper filopodia, dendritic spine, and excitatory synapse development. Knockdown of MST3 in layer 2/3 pyramidal neurons via in utero electroporation also reduced spine density in vivo. Using chemical genetics, we discovered thirteen candidate MST3 substrates and identified the phosphorylation sites. Among the identified MST3 substrates, TAO kinases regulate dendritic filopodia and spine development, similar to MST3. Furthermore, using stable isotope labeling by amino acids in culture (SILAC), we show that phosphorylated TAO1/2 associates with Myosin Va and is necessary for its dendritic localization, thus revealing a mechanism for excitatory synapse development in the mammalian CNS.

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Authors
Ultanir, S. K., Yadav, S., Hertz, N. T., Oses-Prieto, J. A., Claxton, S., Burlingame, A. L., Shokat, K. M., Jan, L. Y., & Jan, Y.-N.
Affiliations
  • University of California, San Francisco (US)
  • Howard Hughes Medical Institute (US)
  • National Institute for Medical Research (GB)
Corresponding author
  • Ultanir, Sila K.
  • Jan, Yuh-Nung
ORCID
Venue
Neuron
Publisher
Elsevier BV
Published
2014-12
Volume
84
Issue
5
Pages
968-982
ISSN
0896-6273 (ISSN-L)
DOI
10.1016/j.neuron.2014.10.025
PMC
PMC4407996
OpenAlex
W2073203830
Cited by
75
References
1
Citations by year
2026: 2 · 2025: 5 · 2024: 7 · 2023: 12 · 2022: 5 · 2021: 7 · 2020: 9 · 2019: 6 · 2018: 11 · 2017: 6 · 2016: 3 · 2015: 1
FWCI
1.52
Type
journal article
Language
en
Open access
Licence
Locations
  • Neuron (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • Howard Hughes Medical Institute
  • National Institutes of Health (5r01eb001987-15)
  • University of California, San Francisco
  • National Institute of Mental Health (R01MH084234)
  • National Institute of General Medical Sciences (T32GM064337, P41GM103481)
  • National Institute of Neurological Disorders and Stroke (R37NS040929)
  • National Institute of Biomedical Imaging and Bioengineering (R01-EB001987)
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
myosin Va, dendritic spine development, dendritic filopodia, protein phosphorylation, kinase substrates, pyramidal neurons, hippocampus, axon growth, chemical genetics
MeSH terms
Hippo Kinases, Age Factors, Animals, Cells, Cultured, Embryo, Mammalian, Hippocampus, Humans, Microtubule-Associated Proteins, Mutation, Neurons, Phosphorylation, Synapses, Protein Serine-Threonine Kinases, Gene Expression Regulation, Developmental, Myosin Heavy Chains, Rats, Long-Evans, MAP Kinase Kinase Kinases, Myosin Type V, RNA, Small Interfering, Dendritic Spines, Rats

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