Calsyntenin-1 is a transmembrane cargo-docking protein important for kinesin-1-mediated fast transport of membrane-bound organelles that exhibits peak expression levels at postnatal day 7. However, ...its neuronal function during postnatal development remains unknown. We generated a knock-out mouse to characterize calsyntenin-1 function in juvenile mice. In the absence of calsyntenin-1, synaptic transmission was depressed. To address the mechanism, evoked EPSPs were analyzed revealing a greater proportion of synaptic GluN2B subunit-containing receptors typical for less mature synapses. This imbalance was due to a disruption in calsyntenin-1-mediated dendritic transport of NMDA receptor subunits. As a consequence of increased expression of GluN2B subunits, NMDA receptor-dependent LTP was enhanced at Schaffer collateral-CA1 pyramidal cell synapses. Interestingly, these defects were accompanied by a decrease in dendritic arborization and increased proportions of immature filopodia-like dendritic protrusions at the expense of thin-type dendritic spines in CA1 pyramidal cells. Thus, these results highlight a key role for calsyntenin-1 in the transport of NMDA receptors to synaptic targets, which is necessary for the maturation of neuronal circuits during early development.
The NA60 experiment at the CERN SPS has studied low-mass muon pairs in 158 AGeV In-In collisions. A strong excess of pairs is observed above the yield expected from neutral meson decays. After ...subtraction of the decay sources, the shape of the resulting mass spectrum is largely consistent with a dominant contribution from
π
+
π
−
→
ρ
→
μ
+
μ
−
annihilation. The associated
ρ spectral function exhibits considerable broadening, but essentially no shift in mass. The acceptance-corrected
p
T
spectra have a shape atypical for radial flow. They also significantly depend on mass, pointing to different sources in different mass regions. Both mass and
p
T
spectra are compared to recent theoretical predictions.
We have identified two novel postsynaptic membrane proteins that are highly similar to calsyntenin-1 in their extracellular parts but vary considerably in their cytoplasmic segment. Calsyntenin-1 has ...recently been identified in our lab as a postsynaptic membrane protein with a highly acidic cytoplasmic segment with putative Ca
2+-binding capacity (Vogt
et al., 2001,
Mol. Cell. Neurosci. 17: 151–166). Based on their structural similarity to calsyntenin-1, we have called the novel proteins calsyntenin-2 and -3, respectively. By immunoelectron microscopy, the calsyntenin protein family was localized in the postsynaptic membrane of excitatory central nervous system (CNS) synapses.
In situ hybridization analysis revealed that calsyntenin-1 was abundant in most neurons of the CNS with relatively little variation in its expression level. Calsyntenin-2 and -3 expressions varied much more with highest levels in GABAergic neurons. Based on their distinct expression patterns and the differences in their cytoplasmic segments, we suggest a cell-type-specific functional role for the three calsyntenins in excitatory synaptic transmission.
Key Words: calsyntenin-1; calsyntenin-2; calsyntenin-3; calcium-binding protein; calcium signaling; synapse; synaptic protein; plasticity.
Hippocampal neurons in culture develop morphological polarity in a sequential pattern; axons form before dendrites. Molecular differences, particularly those of membrane proteins, underlie the ...functional polarity of these domains, yet little is known about the temporal relationship between membrane protein polarization and morphological polarization. We took advantage of viral expression systems to determine when during development the polarization of membrane proteins arises. All markers were unpolarized in neurons before axonogenesis. In neurons with a morphologically distinguishable axon, even on the first day in culture, both axonal and dendritic proteins were polarized. The degree of polarization at these early stages was somewhat less than in mature cells and varied from cell to cell. The cellular mechanism responsible for the polarization of the dendritic marker protein transferrin receptor (TfR) in mature cells centers on directed transport to the dendritic domain. To examine the relationship between cell surface polarization and transport, we assessed the selectivity of transport by live cell imaging. TfR-green fluorescent protein-containing vesicles were already preferentially transported into dendrites at 2 days, the earliest time point we could measure. The selectivity of transport also varied somewhat among cells, and the amount of TfR-green fluorescent protein fluorescence on intracellular structures within the axon correlated with the amount of cell surface expression. This observation implies that selective microtubule-based transport is the primary mechanism that underlies the polarization of TfR on the cell surface. By 5 days in culture, the extent of polarization on the cell surface and the selectivity of transport reached mature levels.
Familial encephalopathy with neuroserpin inclusion bodies is a recently described neurodegenerative disease that is responsible for progressive myoclonic epilepsy or presenile dementia. In a French ...family with the S52R mutation of the neuroserpin gene, progressive myoclonic epilepsy was associated with a frontal syndrome. The typical cerebral inclusions (Collins bodies) were abundant in the frontal cortex and in the head of the caudate nucleus but spared the cerebellum.
We have identified and chromatographically purified an axonally secreted glycoprotein of CNS and PNS neurons. Several peptides derived from it were microsequenced. Based on these sequences, a ...fragment of the corresponding cDNA was amplified and used as a probe to isolate a full length cDNA from a chicken brain cDNA library. Because the deduced amino acid sequence qualified the protein as a novel member of the serpin family of serine protease inhibitors, we called it neuroserpin. Analysis of the primary structural features further characterized neuroserpin as a heparin‐independent, functional inhibitor of a trypsin‐like serine protease. In situ hybridization revealed a predominantly neuronal expression during the late stages of neurogenesis and in the adult brain in regions which exhibit synaptic plasticity. Thus, neuroserpin might function as an axonally secreted regulator of the local extracellular proteolysis involved in the reorganization of the synaptic connectivity during development and synapse plasticity in the adult.
The NA60 experiment at the CERN SPS has studied low-mass muon pairs in 158 A GeV In–In collisions. A strong excess of pairs is observed above the yield expected from neutral meson decays. The ...unprecedented sample size close to 400000 events and the good mass resolution of about 2% made it possible to isolate the excess by subtraction of the decay sources. The shape of the resulting mass spectrum shows some non-trivial centrality dependence, but is largely consistent with a dominant contribution from π+π-→ϱ→μ+μ- annihilation. The associated ϱ spectral function exhibits considerable broadening, but essentially no shift in mass. The pT-differential mass spectra show the excess to be much stronger at low pT than at high pT. The results are compared to theoretical model predictions; they tend to rule out models linking hadron masses directly to the chiral condensate.
The NA60 experiment at the CERN SPS has studied $\phi$ meson production in In-In collisions at 158A GeV via both the $K^+K^-$ and the $\mu^+\mu^-$ decay channels. The yields and inverse slope ...parameters of the $m_T$ spectra observed in the two channels are compatible within errors, different from the large discrepancies seen in Pb-Pb collisions between the hadronic (NA49) and dimuon (NA50) decay channels. Possible physics implications are discussed.
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