The polarity protein PAR-3 and TIAM1 cooperate in dendritic spine morphogenesis
Abstract
PAR-3 (partitioning-defective gene 3) is essential for cell polarization in many contexts, including axon specification. However, polarity proteins have not been implicated in later steps of neuronal differentiation, such as dendritic spine morphogenesis. Here, we show that PAR-3 is necessary for normal spine development in primary hippocampal neurons. Depletion of PAR-3 causes the formation of multiple filopodia- and lamellipodia-like dendritic protrusions - a phenotype similar to neurons expressing activated Rac. PAR-3 regulates spine formation by binding the Rac guanine nucleotide-exchange factor (GEF) TIAM1, and spatially restricting it to dendritic spines. Thus, a balance of PAR-3 and TIAM1 is essential to modulate Rac-GTP levels and to allow spine morphogenesis.
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The reduced spine formation with IDOL overexpression and increased filopodia with IDOL knockout are reminiscent of phenotypes caused by inactivation or constitutive activation of Rac1, respectively.
“The reduced spine formation observed with IDOL overexpression, and the increased proportion of filopodia with IDOL knockout, are reminiscent of phenotypes caused by inactivation or constitutive activation of the GTPase Rac1, respectively (Nakayama et al., 2000; Zhang and Macara, 2006).”
From The E3 ubiquitin ligase IDOL regulates synaptic ApoER2 levels and is important for plasticity and learning (2017) · cites this paper as Zhang and Macara, 2006
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Hippocampal Neuronal Polarity Specified by Spatially Localized mPar3/mPar6 and PI 3-Kinase Activity
Shi, S.-H., Jan, L. Y., & Jan, Y.-N. (2003) · Cell · doi:10.1016/s0092-8674(02)01249-7 · Cited by 600 · see citing works
Macara, I. G. (2004) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1332 · Cited by 341 · see citing works
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Regulation of Synaptic Structure and Function by FMRP-Associated MicroRNAs miR-125b and miR-132
Edbauer, D., Neilson, J. R., Foster, K. A., Wang, C.-F., Seeburg, D. P., Batterton, M. N., Tada, T., Dolan, B. M., Sharp, P. A., & Sheng, M. (2010) · Neuron · doi:10.1016/j.neuron.2010.01.005 · Cited by 735 · see citing works
O'Dushlaine, C., Kenny, E., Heron, E., Donohoe, G., Gill, M., Morris, D., The International Schizophrenia Consortium, & Corvin, A. (2011) · Molecular Psychiatry · doi:10.1038/mp.2010.7 · Cited by 228 · see citing works
Dynamic Control of Excitatory Synapse Development by a Rac1 GEF/GAP Regulatory Complex
Um, K., Niu, S., Duman, J. G., Cheng, J. X., Tu, Y.-K., Schwechter, B., Liu, F., Hiles, L., Narayanan, A. S., Ash, R. T., et al. (2014) · Developmental Cell · doi:10.1016/j.devcel.2014.05.011 · Cited by 81 · see citing works
Chen, S., Chen, J., Shi, H., Wei, M., Castaneda-Castellanos, D. R., Bultje, R. S., Pei, X., Kriegstein, A. R., Zhang, M., & Shi, S.-H. (2013) · Developmental Cell · doi:10.1016/j.devcel.2012.11.014 · Cited by 82 · see citing works
NOS1AP associates with Scribble and regulates dendritic spine development
Richier, L., Williton, K., Clattenburg, L., Colwill, K., O'Brien, M., Tsang, C., Kolar, A., Zinck, N., Metalnikov, P., Trimble, W. S., et al. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.3726-09.2010 · Cited by 81 · see citing works
Loss of correlations among proteins in brains of the Ts65Dn mouse model of down syndrome
Ahmed, M. M., Sturgeon, X., Ellison, M., Davisson, M. T., & Gardiner, K. J. (2012) · Journal of Proteome Research · doi:10.1021/pr2011582 · Cited by 39 · see citing works
Gao, J., Marosi, M., Choi, J., Achiro, J. M., Kim, S., Li, S., Otis, K., Martin, K. C., Portera-Cailliau, C., & Tontonoz, P. (2017) · eLife · doi:10.7554/elife.29178 · Cited by 30 · see citing works
- Authors
- Zhang, H., & Macara, I. G.
- Affiliations
- University of Virginia (US)
- Corresponding author
- Zhang, Huaye
- ORCID
- Macara, Ian G.
- Venue
- Nature Cell Biology
- Published
- 2006-02-12
- Volume
- 8
- Issue
- 3
- Pages
- 227-237
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- OpenAlex
- W2010850820
- Cited by
- 213
- References
- 2
- Citations by year
- 2025: 2 · 2024: 3 · 2022: 16 · 2021: 4 · 2020: 5 · 2019: 10 · 2018: 7 · 2017: 12 · 2016: 9 · 2015: 13 · 2014: 10 · 2013: 23 · 2012: 17
- FWCI
- 6.21
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of General Medical Sciences (GM 070902, R01GM070902)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- 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
- Keywords
- Par3, Tiam1, dendritic spine morphogenesis, neuronal polarity, Rac GTPase, guanine nucleotide exchange factor, hippocampal neurons, filopodia, lamellipodia, axon specification, neuronal differentiation
- MeSH terms
- T-Lymphoma Invasion and Metastasis-inducing Protein 1, Animals, Carrier Proteins, Cell Differentiation, Cells, Cultured, Embryo, Mammalian, Hippocampus, Morphogenesis, Neoplasm Proteins, Nerve Tissue Proteins, Pseudopodia, Synapsins, Cell Polarity, Guanine Nucleotide Exchange Factors, rac GTP-Binding Proteins, Dendritic Spines, Rats
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