TY  - JOUR
AU  - Angel, Del
AU  - Tsutiya, Atsuhiro
AU  - Hayani, Hussam
AU  - Madencioglu, Deniz
AU  - Kul, Emre
AU  - Caliskan, Gürsel
AU  - Demiray, Yunus Emre
AU  - Dityatev, Alexander
AU  - Stork, Oliver
TI  - The Serine/Threonine Kinase NDR2 Regulates Integrin Signaling, Synapse Formation, and Synaptic Plasticity in the Hippocampus.
JO  - Journal of neurochemistry
VL  - 169
IS  - 6
SN  - 0022-3042
CY  - Oxford
PB  - Wiley-Blackwell
M1  - DZNE-2025-00657
SP  - e70094
PY  - 2025
AB  - Nuclear Dbf2-related (NDR) kinases are core components of the Hippo pathway, which controls neuronal polarity and neurite growth in the central nervous system (CNS). NDR2 is the principal NDR kinase in the mouse CNS, where it has been shown to regulate integrin-dependent dendritic branching as well as growth and plasticity in hippocampal mossy fibers. Given the well-established involvement of integrins in plasticity, we hypothesized that NDR2 might regulate synapse formation and plasticity through integrin-mediated mechanisms. In this study, using constitutive NDR2 null mutant mice, we demonstrate that Ndr2 deficiency leads to a reduction of T788/789 phosphorylated β1 integrin expression at synaptic sites both in the hippocampal area CA1 and in primary hippocampal neurons in vitro. This reduction is associated with decreased synaptic density in both conditions and accompanied by reduced long-term potentiation in the synapses between Schaffer collaterals/commissural fibers and CA1 pyramidal cells, which could be restored by activation of integrins with an arginine-glycine-aspartate-containing peptide, as well as with mild spatial memory deficits. Together, our results suggest that NDR2 is involved in integrin-dependent synapse formation and plasticity in the mouse hippocampus.
KW  - Animals
KW  - Protein Serine-Threonine Kinases: genetics
KW  - Protein Serine-Threonine Kinases: physiology
KW  - Protein Serine-Threonine Kinases: metabolism
KW  - Neuronal Plasticity: physiology
KW  - Synapses: physiology
KW  - Mice
KW  - Hippocampus: cytology
KW  - Hippocampus: physiology
KW  - Hippocampus: metabolism
KW  - Signal Transduction: physiology
KW  - Mice, Knockout
KW  - Mice, Inbred C57BL
KW  - Cells, Cultured
KW  - Male
KW  - Integrins: metabolism
KW  - Integrin beta1: metabolism
KW  - Neurons
KW  - hippocampus (Other)
KW  - integrin signaling (Other)
KW  - nuclear DBF2‐related kinase 2 (Other)
KW  - plasticity (Other)
KW  - spatial memory (Other)
KW  - synapses (Other)
KW  - Protein Serine-Threonine Kinases (NLM Chemicals)
KW  - Integrins (NLM Chemicals)
KW  - Integrin beta1 (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:40439020
C2  - pmc:PMC12120816
DO  - DOI:10.1111/jnc.70094
UR  - https://pub.dzne.de/record/278931
ER  -