| First Authors | Takashi Namba |
|---|---|
| Authors | Takashi Namba, Judit Dóczi, Anneline Pinson, Lei Xing, Nereo Kalebic, Michaela Wilsch-Bräuninger, Katherine S. Long, Samir Vaid, Janelle Lauer, Aliona Bogdanova, Barbara Borgonovo, Anna Shevchenko, Patrick Keller, David N. Drechsel, Teymuras V. Kurzchalia, Pauline Wimberger, Christos Chinopoulos, Wieland Huttner |
| Corresponding Authors | Takashi Namba, Wieland Huttner |
| Last Authors | Wieland Huttner |
| Journal Name | Neuron (Neuron) |
| Volume | 105 |
| Issue | 5 |
| Page Range | 867-881 |
| Open Access | false |
| Print Publication Date | 2020-03-04 |
| Online Publication Date | 2019-12-13 |
| Abstract | The human-specific gene ARHGAP11B is preferentially expressed in neural progenitors of fetal human neocortex and increases abundance and proliferation of basal progenitors (BPs), which have a key role in neocortex expansion. ARHGAP11B has therefore been implicated in the evolutionary expansion of the human neocortex, but its mode of action has been unknown. Here, we show that ARHGAP11B is imported into mitochondria, where it interacts with the adenine nucleotide translocase (ANT) and inhibits the mitochondrial permeability transition pore (mPTP). BP expansion by ARHGAP11B requires its presence in mitochondria, and pharmacological inhibition of ANT function or mPTP opening mimic BP expansion by ARHGAP11B. Searching for the underlying metabolic basis, we find that BP expansion by ARHGAP11B requires glutaminolysis, the conversion of glutamine to glutamate for the tricarboxylic acid (TCA) cycle. Hence, an ARHGAP11B-induced, mitochondria-based effect on BP metabolism that is a hallmark of highly mitotically active cells appears to underlie its role in neocortex expansion. |
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| Affiliated With | Antibody Facility, Huttner, Kurzchalia, Mass Spectrometry, Postdoc first author, Postdoc first male, Postdocs, Protein Expression, Shevchenko, Zerial |
| Selected By | |
| Acknowledged Services | Biomedical Services, Mass Spectrometry, Light Microscopy Facility, Antibody Facility |
| Publication Status | Published |
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| DOI | 10.1016/j.neuron.2019.11.027 |
| PubMed ID | 31883789 |
| WebOfScience Link | WOS:000518860700013 |
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| Display Publisher Download Only | false |
| Visible On MPI-CBG Website | true |
| PDF Downloadable | true |
| Created By | thuem |
| Added Date | 2020-01-10 |
| Last Edited By | herbst |
| Last Edited Date | 2021-06-21 17:24:29.827 |
| Library ID | 7585 |
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| Entry Complete | true |
| eDoc Compliant | true |
| Include in Edoc Report | true |
| In Pure | true |
| Ready for eDoc Export | false |
| Author Affiliations Complete | false |
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