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TAOK2 controls synaptic plasticity and anxiety via ERK and calcium signaling

Wenbo Ma1, Inanna Warnhoff2, Marius Stephan3

  • 1Research Group Cell Signalling, Department of Psychiatry and Psychotherapy, LMU University Hospital, LMU Munich, Nussbaumstr. 7, 80336 Munich, Germany.

Iscience
|November 10, 2025
PubMed

Insights

Loss of thousand and one amino acid kinase 2 (TAOK2) in brain neurons impairs synaptic signaling and connectivity, leading to behavioral issues. This suggests TAOK2 is a potential therapeutic target for neuropsychiatric disorders.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • Thousand and one amino acid kinase 2 (TAOK2) is crucial for neuronal development and function.
  • Dysregulation of TAOK2 is linked to neurodevelopmental and neuropsychiatric conditions like autism and schizophrenia.

Purpose of the Study:

  • To investigate the specific role of TAOK2 in excitatory cortical neurons.
  • To elucidate the molecular mechanisms underlying TAOK2's function in synaptic plasticity and behavior.

Main Methods:

  • Generated an excitatory-neuron-specific conditional knockout mouse model (Taok2 cKO) using Emx1-Cre.
  • Performed pathway profiling, Western blotting, calcium imaging, and single-nucleus RNA sequencing on Taok2 cKO neurons and brains.
  • Assessed behavioral phenotypes using the open field test.

Main Results:

  • Taok2 cKO neurons showed impaired ERK/MAPK and calcium signaling pathways.
  • Reduced synaptic density and connectivity were observed in cultured Taok2 cKO neurons.
  • Taok2 cKO mice displayed anxiety-related behaviors and identified dysregulated gene expression in the medial prefrontal cortex.

Conclusions:

  • TAOK2 is essential for maintaining synaptic signaling and connectivity in excitatory cortical neurons.
  • Loss of TAOK2 disrupts neuronal function and leads to behavioral abnormalities.
  • TAOK2 represents a promising therapeutic target for neuropsychiatric disorders.
Keywords:
Cellular neuroscienceMolecular neuroscienceTranscriptomics

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