TY  - JOUR
AU  - Feurle, Patrick
AU  - Abentung, Andreas
AU  - Cera, Isabella
AU  - Wahl, Nico
AU  - Ablinger, Cornelia
AU  - Bucher, Michael
AU  - Stefan, Eduard
AU  - Sprenger, Simon
AU  - Teis, David
AU  - Fischer, Andre
AU  - Laighneach, Aodán
AU  - Whitton, Laura
AU  - Morris, Derek W
AU  - Apostolova, Galina
AU  - Dechant, Georg
TI  - SATB2-LEMD2 interaction links nuclear shape plasticity to regulation of cognition-related genes.
JO  - The EMBO journal
VL  - 40
IS  - 3
SN  - 1460-2075
CY  - Hoboken, NJ [u.a.]
PB  - Wiley
M1  - DZNE-2021-00992
SP  - e103701
PY  - 2021
AB  - 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.
KW  - ATPases Associated with Diverse Cellular Activities: metabolism
KW  - Animals
KW  - Cell Nucleus: metabolism
KW  - Cell Plasticity
KW  - Cells, Cultured
KW  - Cognition
KW  - Endosomal Sorting Complexes Required for Transport: metabolism
KW  - Gene Regulatory Networks
KW  - HeLa Cells
KW  - Hippocampus: cytology
KW  - Hippocampus: metabolism
KW  - Humans
KW  - Intellectual Disability: genetics
KW  - Intellectual Disability: metabolism
KW  - Male
KW  - Matrix Attachment Region Binding Proteins: chemistry
KW  - Matrix Attachment Region Binding Proteins: genetics
KW  - Matrix Attachment Region Binding Proteins: metabolism
KW  - Membrane Proteins: chemistry
KW  - Membrane Proteins: genetics
KW  - Membrane Proteins: metabolism
KW  - Mice
KW  - Mutation
KW  - Neurons: cytology
KW  - Neurons: metabolism
KW  - Nuclear Envelope: metabolism
KW  - Nuclear Proteins: chemistry
KW  - Nuclear Proteins: genetics
KW  - Nuclear Proteins: metabolism
KW  - Schizophrenia: genetics
KW  - Schizophrenia: metabolism
KW  - Transcription Factors: chemistry
KW  - Transcription Factors: genetics
KW  - Transcription Factors: metabolism
KW  - Vacuolar Proton-Translocating ATPases: metabolism
KW  - SATB2 (Other)
KW  - chromatin (Other)
KW  - human cognitive ability (Other)
KW  - neuronal activity (Other)
KW  - nuclear envelope (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:33319920
C2  - pmc:PMC7849313
DO  - DOI:10.15252/embj.2019103701
UR  - https://pub.dzne.de/record/155832
ER  -