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@ARTICLE{Feurle:155832,
author = {Feurle, Patrick and Abentung, Andreas and Cera, Isabella
and Wahl, Nico and Ablinger, Cornelia and Bucher, Michael
and Stefan, Eduard and Sprenger, Simon and Teis, David and
Fischer, Andre and Laighneach, Aodán and Whitton, Laura and
Morris, Derek W and Apostolova, Galina and Dechant, Georg},
title = {{SATB}2-{LEMD}2 interaction links nuclear shape plasticity
to regulation of cognition-related genes.},
journal = {The EMBO journal},
volume = {40},
number = {3},
issn = {1460-2075},
address = {Hoboken, NJ [u.a.]},
publisher = {Wiley},
reportid = {DZNE-2021-00992},
pages = {e103701},
year = {2021},
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.},
keywords = {ATPases Associated with Diverse Cellular Activities:
metabolism / Animals / Cell Nucleus: metabolism / Cell
Plasticity / Cells, Cultured / Cognition / Endosomal Sorting
Complexes Required for Transport: metabolism / Gene
Regulatory Networks / HeLa Cells / Hippocampus: cytology /
Hippocampus: metabolism / Humans / Intellectual Disability:
genetics / Intellectual Disability: metabolism / Male /
Matrix Attachment Region Binding Proteins: chemistry /
Matrix Attachment Region Binding Proteins: genetics / Matrix
Attachment Region Binding Proteins: metabolism / Membrane
Proteins: chemistry / Membrane Proteins: genetics / Membrane
Proteins: metabolism / Mice / Mutation / Neurons: cytology /
Neurons: metabolism / Nuclear Envelope: metabolism / Nuclear
Proteins: chemistry / Nuclear Proteins: genetics / Nuclear
Proteins: metabolism / Schizophrenia: genetics /
Schizophrenia: metabolism / Transcription Factors: chemistry
/ Transcription Factors: genetics / Transcription Factors:
metabolism / Vacuolar Proton-Translocating ATPases:
metabolism / SATB2 (Other) / chromatin (Other) / human
cognitive ability (Other) / neuronal activity (Other) /
nuclear envelope (Other)},
cin = {AG Fischer},
ddc = {570},
cid = {I:(DE-2719)1410002},
pnm = {352 - Disease Mechanisms (POF4-352)},
pid = {G:(DE-HGF)POF4-352},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:33319920},
pmc = {pmc:PMC7849313},
doi = {10.15252/embj.2019103701},
url = {https://pub.dzne.de/record/155832},
}