Die Rolle von TAOK2 in der Neuronalen Migration

• Antragsteller: Dr. Froylan Calderon de Anda
• Fachliche Zuordnung: Entwicklungsneurobiologie ; Biologische Psychiatrie
• Förderung: Förderung von 2019 bis 2024
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 434353741

• Erstellungsjahr: 2024

Zusammenfassung der Projektergebnisse

Key scientific findings and any potential applications: Our data further support the role of TAOK2 during brain development and its implication in ASD etiology supposedly through impairing neuronal migration during the late mid-fetal phase of cortical development. We show that a gene located in the ASD-associated 16p11.2 locus is associated with translational control. Specifically, we reveal that TAOK2 can act as a repressor regulating protein synthesis at the elongation step.

Projektbezogene Publikationen (Auswahl)

• Altered TAOK2 activity causes autism-related neurodevelopmental and cognitive abnormalities through RhoA signaling. Molecular Psychiatry, 24(9), 1329-1350.
  Richter, Melanie; Murtaza, Nadeem; Scharrenberg, Robin; White, Sean H.; Johanns, Ole; Walker, Susan; Yuen, Ryan K. C.; Schwanke, Birgit; Bedürftig, Bianca; Henis, Melad; Scharf, Sarah; Kraus, Vanessa; Dörk, Ronja; Hellmann, Jakob; Lindenmaier, Zsuzsa; Ellegood, Jacob; Hartung, Henrike; Kwan, Vickie; Sedlacik, Jan ... & Calderon de Anda, Froylan
  
• Male offspring born to mildly ZIKV-infected mice are at risk of developing neurocognitive disorders in adulthood. Nature Microbiology, 3(10), 1161-1174.
  Stanelle-Bertram, Stephanie; Walendy-Gnirß, Kerstin; Speiseder, Thomas; Thiele, Swantje; Asante, Ivy Asantewaa; Dreier, Carola; Kouassi, Nancy Mounogou; Preuß, Annette; Pilnitz-Stolze, Gundula; Müller, Ursula; Thanisch, Stefanie; Richter, Melanie; Scharrenberg, Robin; Kraus, Vanessa; Dörk, Ronja; Schau, Lynn; Herder, Vanessa; Gerhauser, Ingo; Pfankuche, Vanessa Maria ... & Gabriel, Gülsah
  
• Radial F-actin Organization During Early Neuronal Development. openRxiv.
  Meka, Durga Praveen; Scharrenberg, Robin; Zhao, Bing; König, Theresa; Schaefer, Irina; Schwanke, Birgit; Kobler, Oliver; Klykov, Sergei; Richter, Melanie; Eggert, Dennis; Windhorst, Sabine; Dotti, Carlos G.; Kreutz, Michael R.; Mikhaylova, Marina & Calderon de Anda, Froylan
  
• Maintenance of cell type-specific connectivity and circuit function requires Tao kinase. Nature Communications, 10(1).
  Tenedini, Federico Marcello; Sáez, González Maria; Hu, Chun; Pedersen, Lisa Hedegaard; Petruzzi, Mabel Matamala; Spitzweck, Bettina; Wang, Denan; Richter, Melanie; Petersen, Meike; Szpotowicz, Emanuela; Schweizer, Michaela; Sigrist, Stephan J.; Calderon de Anda, Froylan & Soba, Peter
  
• Centrosome-dependent microtubule organization sets the conditions for axon formation. openRxiv.
  Meka, Durga Praveen; Kobler, Oliver; Wuesthoff, Souhaila; Schwanke, Birgit; Krisp, Christoph; Schmuelling, Nessa; Rueter, René; Ruecker, Tabitha; Schlüter, Hartmut; Fornasiero, Eugenio F. & Calderon de Anda, Froylan
  
• Conserved Tao Kinase Activity Regulates Dendritic Arborization, Cytoskeletal Dynamics, and Sensory Function inDrosophila. The Journal of Neuroscience, 40(9), 1819-1833.
  Hu, Chun; Kanellopoulos, Alexandros K.; Richter, Melanie; Petersen, Meike; Konietzny, Anja; Tenedini, Federico M.; Hoyer, Nina; Cheng, Lin; Poon, Carole L.C.; Harvey, Kieran F.; Windhorst, Sabine; Parrish, Jay Z.; Mikhaylova, Marina; Bagni, Claudia; Calderon de Anda, Froylan & Soba, Peter
  
• Neuron-specific protein network mapping of autism risk genes identifies shared biological mechanisms and disease-relevant pathologies. Cell Reports, 41(8), 111678.
  Murtaza, Nadeem; Cheng, Annie A.; Brown, Chad O.; Meka, Durga Praveen; Hong, Shuai; Uy, Jarryll A.; El-Hajjar, Joelle; Pipko, Neta; Unda, Brianna K.; Schwanke, Birgit; Xing, Sansi; Thiruvahindrapuram, Bhooma; Engchuan, Worrawat; Trost, Brett; Deneault, Eric; Calderon de Anda, Froylan; Doble, Bradley W.; Ellis, James; Anagnostou, Evdokia ... & Singh, Karun K.
  
• Pum2 and TDP-43 refine area-specific cytoarchitecture post-mitotically and modulate translation of Sox5, Bcl11b, and Rorb mRNAs in developing mouse neocortex. eLife, 11.
  Harb, Kawssar; Richter, Melanie; Neelagandan, Nagammal; Magrinelli, Elia; Harfoush, Hend; Kuechler, Katrin; Henis, Melad; Hermanns-Borgmeyer, Irm; Calderon de Anda, Froylan & Duncan, Kent
  
• TAOK2 rescues autism-linked developmental deficits in a 16p11.2 microdeletion mouse model. Molecular Psychiatry, 27(11), 4707-4721.
  Scharrenberg, Robin; Richter, Melanie; Johanns, Ole; Meka, Durga Praveen; Rücker, Tabitha; Murtaza, Nadeem; Lindenmaier, Zsuzsa; Ellegood, Jacob; Naumann, Anne; Zhao, Bing; Schwanke, Birgit; Sedlacik, Jan; Fiehler, Jens; Hanganu-Opatz, Ileana L.; Lerch, Jason P.; Singh, Karun K. & Calderon de Anda, Froylan
  
• Protocol for differential multi-omic analyses of distinct cell types in the mouse cerebral cortex. STAR Protocols, 5(1), 102793.
  Meka, Durga Praveen; Richter, Melanie; Rücker, Tabitha; Voss, Hannah; Rissiek, Anne; Krisp, Christoph; Kumar, Nisha Hemandhar; Schwanke, Birgit; Fornasiero, Eugenio F.; Schlüter, Hartmut & Calderon de Anda, Froylan
  
• The autism susceptibility kinase, TAOK2, phosphorylates eEF2 and modulates translation. Science Advances, 10(15).
  Henis, Melad; Rücker, Tabitha; Scharrenberg, Robin; Richter, Melanie; Baltussen, Lucas; Hong, Shuai; Meka, Durga Praveen; Schwanke, Birgit; Neelagandan, Nagammal; Daaboul, Danie; Murtaza, Nadeem; Krisp, Christoph; Harder, Sönke; Schlüter, Hartmut; Kneussel, Matthias; Hermans-Borgmeyer, Irm; de Wit, Joris; Singh, Karun K.; Duncan, Kent E. & Calderon de Anda, Froylan