Journal Article

DZNE-2021-00992

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png SATB2-LEMD2 interaction links nuclear shape plasticity to regulation of cognition-related genes.

Feurle, P. ; Abentung, A. ; Cera, I. ; Wahl, N. ; Ablinger, C. ; Bucher, M. ; Stefan, E. ; Sprenger, S. ; Teis, D. ; Fischer, A.DZNE* ; Laighneach, A. ; Whitton, L. ; Morris, D. W. ; Apostolova, G. ; Dechant, G.

2021
Wiley Hoboken, NJ [u.a.]

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Please use a persistent id in citations: doi:10.15252/embj.2019103701

Abstract: SATB2 is a schizophrenia risk gene and is genetically associated with human intelligence. How it affects cognition at molecular level is currently unknown. Here, we show that interactions between SATB2, a chromosomal scaffolding protein, and the inner nuclear membrane protein LEMD2 orchestrate the response of pyramidal neurons to neuronal activation. Exposure to novel environment in vivo causes changes in nuclear shape of CA1 hippocampal neurons via a SATB2-dependent mechanism. The activity-driven plasticity of the nuclear envelope requires not only SATB2, but also its protein interactor LEMD2 and the ESCRT-III/VPS4 membrane-remodeling complex. Furthermore, LEMD2 depletion in cortical neurons, similar to SATB2 ablation, affects neuronal activity-dependent regulation of multiple rapid and delayed primary response genes. In human genetic data, LEMD2-regulated genes are enriched for de novo mutations reported in intellectual disability and schizophrenia and are, like SATB2-regulated genes, enriched for common variants associated with schizophrenia and cognitive function. Hence, interactions between SATB2 and the inner nuclear membrane protein LEMD2 influence gene expression programs in pyramidal neurons that are linked to cognitive ability and psychiatric disorder etiology.

Keyword(s): ATPases Associated with Diverse Cellular Activities: metabolism (MeSH) ; Animals (MeSH) ; Cell Nucleus: metabolism (MeSH) ; Cell Plasticity (MeSH) ; Cells, Cultured (MeSH) ; Cognition (MeSH) ; Endosomal Sorting Complexes Required for Transport: metabolism (MeSH) ; Gene Regulatory Networks (MeSH) ; HeLa Cells (MeSH) ; Hippocampus: cytology (MeSH) ; Hippocampus: metabolism (MeSH) ; Humans (MeSH) ; Intellectual Disability: genetics (MeSH) ; Intellectual Disability: metabolism (MeSH) ; Male (MeSH) ; Matrix Attachment Region Binding Proteins: chemistry (MeSH) ; Matrix Attachment Region Binding Proteins: genetics (MeSH) ; Matrix Attachment Region Binding Proteins: metabolism (MeSH) ; Membrane Proteins: chemistry (MeSH) ; Membrane Proteins: genetics (MeSH) ; Membrane Proteins: metabolism (MeSH) ; Mice (MeSH) ; Mutation (MeSH) ; Neurons: cytology (MeSH) ; Neurons: metabolism (MeSH) ; Nuclear Envelope: metabolism (MeSH) ; Nuclear Proteins: chemistry (MeSH) ; Nuclear Proteins: genetics (MeSH) ; Nuclear Proteins: metabolism (MeSH) ; Schizophrenia: genetics (MeSH) ; Schizophrenia: metabolism (MeSH) ; Transcription Factors: chemistry (MeSH) ; Transcription Factors: genetics (MeSH) ; Transcription Factors: metabolism (MeSH) ; Vacuolar Proton-Translocating ATPases: metabolism (MeSH) ; SATB2 ; chromatin ; human cognitive ability ; neuronal activity ; nuclear envelope

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Contributing Institute(s):

1. Epigenetics and Systems Medicine in Neurodegenerative Diseases (AG Fischer)

Research Program(s):

1. 352 - Disease Mechanisms (POF4-352) (POF4-352)

Appears in the scientific report 2021

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Wiley ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 10 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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