Nuclear calcium signaling regulates nuclear export of a subset of class IIa histone deacetylases following synaptic activity

• Verfasst von: Schlumm, Friederike [VerfasserIn]
• Verfasst von: Mauceri, Daniela [VerfasserIn]
• Verfasst von: Freitag, H. Eckehard [VerfasserIn]
• Verfasst von: Bading, Hilmar [VerfasserIn]
• Titel: Nuclear calcium signaling regulates nuclear export of a subset of class IIa histone deacetylases following synaptic activity
• Verf.angabe: Friederike Schlumm, Daniela Mauceri, H. Eckehard Freitag, and Hilmar Bading
• Jahr: 2013
• Umfang: 11 S.
• Teil: volume:288
• Teil: year:2013
• Teil: number:12
• Teil: pages:8074-8084
• Teil: extent:11
• Fussnoten: Elektronische Reproduktion der Druck-Ausgabe ; Available online 4 January 2021 ; Gesehen am 01.07.2021
• Titel Quelle: Enthalten in: The journal of biological chemistry
• Ort Quelle: Bethesda, Md. : ASBMB Publications, 1905
• Jahr Quelle: 2013
• Band/Heft Quelle: 288(2013), 12, Seite 8074-8084
• ISSN Quelle: 1083-351X
• DOI: doi:10.1074/jbc.M112.432773
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Calcium Signaling
• Sach-SW: Gene Regulation
• Sach-SW: Histone Deacetylase
• Sach-SW: Neurobiology
• Sach-SW: Nuclear Translocation
• Sach-SW: Signal Transduction
• K10plus-PPN: 1761739352

Abstract

In neurons, dynamic changes in the subcellular localization of histone deacetylases (HDACs) are thought to contribute to signal-regulated gene expression. Here we show that in mouse hippocampal neurons, synaptic activity-dependent nucleo-cytoplasmic shuttling is a common feature of all members of class IIa HDACs, which distinguishes them from other classes of HDACs. Nuclear calcium, a key regulator in neuronal gene expression, is required for the nuclear export of a subset of class IIa HDACs. We found that inhibition of nuclear calcium signaling using CaMBP4 or increasing the nuclear calcium buffering capacity by means of expression of a nuclear targeted version of parvalbumin (PV.NLS-mC) led to a build-up of HDAC4 and HDAC5 in the cell nucleus, which in the case of PV.NLS-mC can be reversed by nuclear calcium transients triggered by bursts of action potential firing. A similar nuclear accumulation of HDAC4 and HDAC5 was observed in vivo in the mouse hippocampus following stereotaxic delivery of recombinant adeno-associated viruses expressing either CaMBP4 or PV.NLS-mC. The modulation of HDAC4 activity either by RNA interference-mediated reduction of HDAC4 protein levels or by expression of a constitutively nuclear localized mutant of HDAC4 leads to changes in the mRNA levels of several nuclear calcium-regulated genes with known functions in acquired neuroprotection (atf3, serpinb2), memory consolidation (homer1, arc), and the development of chronic pain (ptgs2, c1qc). These results identify nuclear calcium as a regulator of nuclear export of HDAC4 and HDAC5. The reduction of nuclear localized HDACs represents a novel transcription-promoting pathway stimulated by nuclear calcium.