Nuclear calcium buffering capacity shapes neuronal architecture

• Verfasst von: Mauceri, Daniela [VerfasserIn]
• Verfasst von: Hertle, Anna M. [VerfasserIn]
• Verfasst von: Schramm, Kathrin [VerfasserIn]
• Verfasst von: Weiss, Ursula [VerfasserIn]
• Verfasst von: Bading, Hilmar [VerfasserIn]
• Titel: Nuclear calcium buffering capacity shapes neuronal architecture
• Verf.angabe: Daniela Mauceri, Anna M. Hagenston, Kathrin Schramm, Ursula Weiss, and Hilmar Bading
• E-Jahr: 2015
• Jahr: July 31, 2015
• Umfang: 11 S.
• Fussnoten: Gesehen am 09.06.2020
• Titel Quelle: Enthalten in: JBC papers in press
• Ort Quelle: Bethesda, MD. : American Soc. for Biochemistry and Molecular Biology, 2003
• Jahr Quelle: 2015
• Band/Heft Quelle: 290(2015), 38, Seite 23039-23049
• ISSN Quelle: 1083-351X
• DOI: doi:10.1074/jbc.M115.654962
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: calcium
• Sach-SW: calcium binding protein
• Sach-SW: dendrite
• Sach-SW: gene expression
• Sach-SW: signal transduction
• Sach-SW: synapse
• K10plus-PPN: 1700216805

Abstract

Calcium-binding proteins (CaBPs) such as parvalbumin are part of the cellular calcium buffering system that determines intracellular calcium diffusion and influences the spatiotemporal dynamics of calcium signals. In neurons, CaBPs are primarily localized to the cytosol and function, for example, in nerve terminals in short-term synaptic plasticity. However, CaBPs are also expressed in the cell nucleus, suggesting that they modulate nuclear calcium signals, which are key regulators of neuronal gene expression. Here we show that the calcium buffering capacity of the cell nucleus in mouse hippocampal neurons regulates neuronal architecture by modulating the expression levels of VEGFD and the complement factor C1q-c, two nuclear calcium-regulated genes that control dendrite geometry and spine density, respectively. Increasing the levels of nuclear calcium buffers by means of expression of a nuclearly targeted form of parvalbumin fused to mCherry (PV.NLS-mC) led to a reduction in VEGFD expression and, as a result, to a decrease in total dendritic length and complexity. In contrast, mRNA levels of the synapse pruning factor C1q-c were increased in neurons expressing PV.NLS-mC, causing a reduction in the density and size of dendritic spines. Our results establish a close link between nuclear calcium buffering capacity and the transcription of genes that determine neuronal structure. They suggest that the development of cognitive deficits observed in neurological conditions associated with CaBP deregulation may reflect the loss of necessary structural features of dendrites and spines.