Autism spectrum disorder susceptibility gene TAOK2 affects basal dendrite formation in the neocortex
How neurons develop their morphology is an important question in neurobiology. Here we describe a new pathway that specifically affects the formation of basal dendrites and axonal projections in cortical pyramidal neurons. We report that thousand-and-one-amino acid 2 kinase (TAOK2), also known as TA...
| Main Authors: | , , , , , , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | en_US |
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Nature Publishing Group
2015
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| Online Access: | http://hdl.handle.net/1721.1/92919 https://orcid.org/0000-0003-1262-0592 https://orcid.org/0000-0001-8426-6188 |
| _version_ | 1826199076454006784 |
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| author | Calderon de Anda, Froylan Rosario, Ana Lucia Durak, Omer Tran, Tracy Meletis, Konstantinos Rei, Damien Soda, Takahiro Madabhushi, Ram Ginty, David D Kolodkin, Alex L Tsai, Li-Huei Graff, Johannes |
| author2 | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences |
| author_facet | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Calderon de Anda, Froylan Rosario, Ana Lucia Durak, Omer Tran, Tracy Meletis, Konstantinos Rei, Damien Soda, Takahiro Madabhushi, Ram Ginty, David D Kolodkin, Alex L Tsai, Li-Huei Graff, Johannes |
| author_sort | Calderon de Anda, Froylan |
| collection | MIT |
| description | How neurons develop their morphology is an important question in neurobiology. Here we describe a new pathway that specifically affects the formation of basal dendrites and axonal projections in cortical pyramidal neurons. We report that thousand-and-one-amino acid 2 kinase (TAOK2), also known as TAO2, is essential for dendrite morphogenesis. TAOK2 downregulation impairs basal dendrite formation in vivo without affecting apical dendrites. Moreover, TAOK2 interacts with Neuropilin 1 (Nrp1), a receptor protein that binds the secreted guidance cue Semaphorin 3A (Sema3A). TAOK2 overexpression restores dendrite formation in cultured cortical neurons from Nrp1[superscript Sema−] mice, which express Nrp1 receptors incapable of binding Sema3A. TAOK2 overexpression also ameliorates the basal dendrite impairment resulting from Nrp1 downregulation in vivo. Finally, Sema3A and TAOK2 modulate the formation of basal dendrites through the activation of the c-Jun N-terminal kinase (JNK). These results delineate a pathway whereby Sema3A and Nrp1 transduce signals through TAOK2 and JNK to regulate basal dendrite development in cortical neurons. |
| first_indexed | 2024-09-23T11:14:03Z |
| format | Article |
| id | mit-1721.1/92919 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T11:14:03Z |
| publishDate | 2015 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/929192022-10-01T02:14:55Z Autism spectrum disorder susceptibility gene TAOK2 affects basal dendrite formation in the neocortex Calderon de Anda, Froylan Rosario, Ana Lucia Durak, Omer Tran, Tracy Meletis, Konstantinos Rei, Damien Soda, Takahiro Madabhushi, Ram Ginty, David D Kolodkin, Alex L Tsai, Li-Huei Graff, Johannes Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Picower Institute for Learning and Memory Calderon de Anda, Froylan Rosario, Ana Lucia Durak, Omer Graff, Johannes Meletis, Konstantinos Rei, Damien Soda, Takahiro Madabhushi, Ram Tsai, Li-Huei How neurons develop their morphology is an important question in neurobiology. Here we describe a new pathway that specifically affects the formation of basal dendrites and axonal projections in cortical pyramidal neurons. We report that thousand-and-one-amino acid 2 kinase (TAOK2), also known as TAO2, is essential for dendrite morphogenesis. TAOK2 downregulation impairs basal dendrite formation in vivo without affecting apical dendrites. Moreover, TAOK2 interacts with Neuropilin 1 (Nrp1), a receptor protein that binds the secreted guidance cue Semaphorin 3A (Sema3A). TAOK2 overexpression restores dendrite formation in cultured cortical neurons from Nrp1[superscript Sema−] mice, which express Nrp1 receptors incapable of binding Sema3A. TAOK2 overexpression also ameliorates the basal dendrite impairment resulting from Nrp1 downregulation in vivo. Finally, Sema3A and TAOK2 modulate the formation of basal dendrites through the activation of the c-Jun N-terminal kinase (JNK). These results delineate a pathway whereby Sema3A and Nrp1 transduce signals through TAOK2 and JNK to regulate basal dendrite development in cortical neurons. Simons Foundation Massachusetts Institute of Technology. Simons Center for the Social Brain (Postdoctoral Fellowship) 2015-01-15T21:30:19Z 2015-01-15T21:30:19Z 2012-06 2012-03 Article http://purl.org/eprint/type/JournalArticle 1097-6256 1546-1726 http://hdl.handle.net/1721.1/92919 Calderon de Anda, Froylan, Ana Lucia Rosario, Omer Durak, Tracy Tran, Johannes Gräff, Konstantinos Meletis, Damien Rei, et al. “Autism Spectrum Disorder Susceptibility Gene TAOK2 Affects Basal Dendrite Formation in the Neocortex.” Nat Neurosci 15, no. 7 (June 10, 2012): 1022–1031. https://orcid.org/0000-0003-1262-0592 https://orcid.org/0000-0001-8426-6188 en_US http://dx.doi.org/10.1038/nn.3141 Nature Neuroscience Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Nature Publishing Group PMC |
| spellingShingle | Calderon de Anda, Froylan Rosario, Ana Lucia Durak, Omer Tran, Tracy Meletis, Konstantinos Rei, Damien Soda, Takahiro Madabhushi, Ram Ginty, David D Kolodkin, Alex L Tsai, Li-Huei Graff, Johannes Autism spectrum disorder susceptibility gene TAOK2 affects basal dendrite formation in the neocortex |
| title | Autism spectrum disorder susceptibility gene TAOK2 affects basal dendrite formation in the neocortex |
| title_full | Autism spectrum disorder susceptibility gene TAOK2 affects basal dendrite formation in the neocortex |
| title_fullStr | Autism spectrum disorder susceptibility gene TAOK2 affects basal dendrite formation in the neocortex |
| title_full_unstemmed | Autism spectrum disorder susceptibility gene TAOK2 affects basal dendrite formation in the neocortex |
| title_short | Autism spectrum disorder susceptibility gene TAOK2 affects basal dendrite formation in the neocortex |
| title_sort | autism spectrum disorder susceptibility gene taok2 affects basal dendrite formation in the neocortex |
| url | http://hdl.handle.net/1721.1/92919 https://orcid.org/0000-0003-1262-0592 https://orcid.org/0000-0001-8426-6188 |
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