Dataset Information

Mechanical control of nuclear import by Importin-7 is regulated by its dominant cargo YAP

ABSTRACT: Mechanical control of nuclear import by Importin-7 is regulated by its dominant cargo YAP

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Enrique Calvo

LAB HEAD: Enrique Calvo

PROVIDER: PXD025910 | Pride | 2022-04-04

REPOSITORIES: Pride

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Publications

Mechanical control of nuclear import by Importin-7 is regulated by its dominant cargo YAP.

García-García María M Sánchez-Perales Sara S Jarabo Patricia P Calvo Enrique E Huyton Trevor T Fu Liran L Ng Sheung Chun SC Sotodosos-Alonso Laura L Vázquez Jesús J Casas-Tintó Sergio S Görlich Dirk D Echarri Asier A Del Pozo Miguel A MA

Nature communications 20220304 1

Mechanical forces regulate multiple essential pathways in the cell. The nuclear translocation of mechanoresponsive transcriptional regulators is an essential step for mechanotransduction. However, how mechanical forces regulate the nuclear import process is not understood. Here, we identify a highly mechanoresponsive nuclear transport receptor (NTR), Importin-7 (Imp7), that drives the nuclear import of YAP, a key regulator of mechanotransduction pathways. Unexpectedly, YAP governs the mechanores ...[more]

PMID: 35246520

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Project description:Introduction: The mechanisms governing synaptonuclear transport, and the transcriptional pathways that are at the core of neuronal disorders are poorly understood. The importin family of nuclear import factors has pivotal roles in such pathways, due to their involvement in intracellular transport from both synapse to soma and cytoplasm to nucleus. Mammals express six different isoforms of importin α, which bind an Importin β to form transport complexes for specific cargoes. Methods: We addressed the roles of importin α isoforms in mammalian CNS by evaluation of a systematic series of importin α knockout mice. A comprehensive battery of behavioral tests was used to investigate spontaneous and novelty-induced locomotion, basal ganglia function, motor coordination, neuromuscular integration, anxiety-related behaviors and memory. Subsequent analyses using acute-brain slice electrophysiology, RNA-seq, bioinformatics, imaging and pharmacology was used in order to delineate the contribution of genes and signaling pathways involved in the identified phenotype and screen for new therapeutic approaches. Results and Discussion: During the course of comprehensive behavioral profiling of importin α mouse mutants, we identified an importin α knockout (KO) mouse with significantly reduced anxiety levels. Electrophysiological recordings in acute hippocampal slices showed a reduced short-term and presynaptic plasticity (paired-pulse facilitation deficit, lower PTP), while LTP was not affected in these mutants. We then performed transcriptional profiling (RNA-seq) from hippocampal extracts of wild type versus mutant animals after exposure to an anxiogenic drug. Computational analysis revealed differences in the expression of genes and the involvement of transcription factors. Drugs that activate LXR or the Sphingosine 1 phosphate receptor have robust anxiolytic effects, while a Sphk1 blocker reverses anxiolysis in the importin α5 knockout mouse. Thus, importin α5 influences anxiety by regulating nuclear import in neurons.

Dataset Information

Mechanical control of nuclear import by Importin-7 is regulated by its dominant cargo YAP

Publications

Mechanical control of nuclear import by Importin-7 is regulated by its dominant cargo YAP.

Similar Datasets

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