Daniela Mauceri

Publications (10) View all

• Article: Nuclear calcium-VEGFD signaling controls maintenance of dendrite arborization necessary for memory formation.

  Daniela Mauceri, H Eckehard Freitag, Ana M M Oliveira, C Peter Bengtson, Hilmar Bading
  [show abstract] [hide abstract]
  ABSTRACT: The role of neuronal dendrites is to receive and process synaptic inputs. The geometry of the dendritic arbor can undergo neuronal activity-dependent changes that may impact the cognitive abilities of the organism. Here we show that vascular endothelial growth factor D (VEGFD), commonly known as an angiogenic mitogen, controls the total length and complexity of dendrites both in cultured hippocampal neurons and in the adult mouse hippocampus. VEGFD expression is dependent upon basal neuronal activity and requires nuclear calcium-calmodulin-dependent protein kinase IV (CaMKIV) signaling. Suppression of VEGFD expression in the mouse hippocampus by RNA interference causes memory impairments. Thus, nuclear calcium-VEGFD signaling mediates the effect of neuronal activity on the maintenance of dendritic arbors in the adult hippocampus and is required for cognitive functioning. These results suggest that caution be employed in the clinical use of blockers of VEGFD signaling for antiangiogenic cancer therapy.
  Neuron 07/2011; 71(1):117-30. · 14.74 Impact Factor
• Article: Decreased NR2B subunit synaptic levels cause impaired long-term potentiation but not long-term depression.

  Fabrizio Gardoni, Daniela Mauceri, Matteo Malinverno, Federica Polli, Cinzia Costa, Alessandro Tozzi, Sabrina Siliquini, Barbara Picconi, Flaminio Cattabeni, Paolo Calabresi, Monica Di Luca
  [show abstract] [hide abstract]
  ABSTRACT: The discovery of the molecular mechanisms regulating the abundance of synaptic NMDA receptors is essential for understanding how synaptic plasticity, as well as excitotoxic events, are regulated. However, a complete understanding of the precise molecular mechanisms regulating the composition of the NMDA receptor complex at hippocampal synapse is still missing. Here, we show that 2 h of CaMKII inhibition leads to a specific reduction of synaptic NR2B-containing NMDA receptors without affecting localization of the NR2A subunit; this molecular event is accompanied by a dramatic reduction in the induction of long-term potentiation (LTP), while long-term depression induction is unaffected. The same molecular and functional results were obtained by disrupting NR2B/PSD-95 complex with NR2B C-tail cell permeable peptide (TAT-2B). These data indicate that NR2B redistribution between synaptic and extrasynaptic membranes represents an important molecular disturbance of the glutamatergic synapse and affects the correct induction of LTP.
  Journal of Neuroscience 02/2009; 29(3):669-77. · 7.11 Impact Factor
• Article: Dual role of CaMKII-dependent SAP97 phosphorylation in mediating trafficking and insertion of NMDA receptor subunit NR2A.

  D Mauceri, F Gardoni, E Marcello, M Di Luca
  [show abstract] [hide abstract]
  ABSTRACT: Synapse Associated Protein 97 (SAP97), a member of membrane-associated guanylate kinase (MAGUK) protein family, has been involved in the correct targeting and clustering of ionotropic glutamate receptors (iGluRs) at postsynaptic sites. Calcium/calmodulin kinase II (CaMKII) phosphorylates SAP97 on two major sites in vivo; one located in the N-terminal domain (Ser39) and the other in the first postsynaptic density disc large ZO1 (PDZ) domain (Ser232). CaMKII-mediated phosphorylation of SAP97-Ser39 is necessary and sufficient to drive SAP97 to the postsynaptic compartment in cultured hippocampal neurons. CaMKII-dependent phosphorylation of Ser232 disrupts SAP97 interaction with NR2A subunit, thereby regulating synaptic targeting of this NMDA receptor subunit. Here we show by means of phospho-specific antibodies that SAP97-Ser39 phosphorylation represents the driving force to release SAP97/NR2A complex from the endoplasmic reticulum. Ser39 phosphorylation does not interfere with SAP97 capability to bind NR2A. On the contrary, SAP97-Ser232 phosphorylation occurs within the postsynaptic compartment and is responsible for both the disruption of NR2A/SAP97 complex and, consequently, for NR2A insertion in the postsynaptic membrane. Thus, CaMKII-dependent phosphorylation of SAP97 in different time frames and locations within the neurons controls both NR2A trafficking and insertion.
  Journal of Neurochemistry 03/2007; 100(4):1032-46. · 4.06 Impact Factor
• Article: Nuclear calcium signaling regulates nuclear export of a subset of class IIa histone deacetylases following synaptic activity.

  Friederike Schlumm, Daniela Mauceri, H Eckehard Freitag, Hilmar Bading
  [show abstract] [hide abstract]
  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 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.
  Journal of Biological Chemistry 01/2013; · 4.77 Impact Factor
• Article: Nuclear calcium signaling in spinal neurons drives a genomic program required for persistent inflammatory pain.

  Manuela Simonetti, Anna M Hagenston, Daniel Vardeh, H Eckehard Freitag, Daniela Mauceri, Jianning Lu, Venkata P Satagopam, Reinhard Schneider, Michael Costigan, Hilmar Bading, Rohini Kuner
  [show abstract] [hide abstract]
  ABSTRACT: Persistent pain induced by noxious stimuli is characterized by the transition from normosensitivity to hypersensitivity. Underlying mechanisms are not well understood, although gene expression is considered important. Here, we show that persistent nociceptive-like activity triggers calcium transients in neuronal nuclei within the superficial spinal dorsal horn, and that nuclear calcium is necessary for the development of long-term inflammatory hypersensitivity. Using a nucleus-specific calcium signal perturbation strategy in vivo complemented by gene profiling, bioinformatics, and functional analyses, we discovered a pain-associated, nuclear calcium-regulated gene program in spinal excitatory neurons. This includes C1q, a modulator of synaptic spine morphogenesis, which we found to contribute to activity-dependent spine remodelling on spinal neurons in a manner functionally associated with inflammatory hypersensitivity. Thus, nuclear calcium integrates synapse-to-nucleus communication following noxious stimulation and controls a spinal genomic response that mediates the transition between acute and long-term nociceptive sensitization by modulating functional and structural plasticity.
  Neuron 01/2013; 77(1):43-57. · 14.74 Impact Factor