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Mutations in the postsynaptic signaling hub TNIK disrupts neuronal progenitor cells and immature neuronal function in human models of neurodevelopmental disease

ABSTRACT: Synaptic proteins, in particular those connected in large protein interaction networks at the postsynaptic site of glutamatergic neurons have been associated to a number of neurodevelopmental disorders. While their contribution to disease has been well documented in mature rodent synapses, their role in early neuronal development and in non-neuronal cell types is not known. Additionally, it is unclear if they are associated in the same protein interaction networks (PINs) in early neuronal development, particularly in human models of neurodevelopmental disease. Here we use the postsynaptic density (PSD) protein TNIK as a model of a classical PSD signaling hub associated to neurodevelopmental disease. Using hiPSC models of TNIK disfunction and disease, we show that PSD PINs are dysregulated by TNIK in immature neurons, synapses and neuronal progenitor cells (NPCs). TNIK impairs NPCs and human immature synapses using different signaling mechanisms and associating to different sets of “PSD proteins”.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Generation Of Neurons, Cell Culture

SUBMITTER: marcelo coba

LAB HEAD: Marcelo Coba

PROVIDER: PXD035004 | Pride | 2024-03-26

REPOSITORIES: Pride

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