Implications of the N-terminal heterogeneity for the neuronal K-Cl cotransporter KCC2 function

Peer reviewe

In vivo Calcium Imaging of Evoked Calcium Waves in the Embryonic Cortex

The dynamics of intracellular calcium fluxes are instrumental in the proliferation, differentiation, and migration of neuronal cells. Knowledge thus far of the relationship between these calcium changes and physiological processes in the developing brain has derived principally from ex vivo and in vitro experiments. Here, we present a new method to image intracellular calcium flux in the cerebral cortex of live rodent embryos, whilst attached to the dam through the umbilical cord. Using this approach we demonstrate induction of calcium waves by laser stimulation. These waves are sensitive to ATP-receptor blockade and are significantly increased by pharmacological facilitation of intracellular-calcium release. This approach is the closest to physiological conditions yet achieved for imaging of calcium in the embryonic brain and as such opens new avenues for the study of prenatal brain development. Furthermore, the developed method could open the possibilities of preclinical translational studies in embryos particularly important for developmentally related diseases such as schizophrenia and autism.Peer reviewe

HB-GAM (pleiotrophin) reverses inhibition of neural regeneration by the CNS extracellular matrix

Chondroitin sulfate (CS) glycosaminoglycans inhibit regeneration in the adult central nervous system (CNS). We report here that HB-GAM (heparin-binding growth-associated molecule; also known as pleiotrophin), a CS-binding protein expressed at high levels in the developing CNS, reverses the role of the CS chains in neurite growth of CNS neurons in vitro from inhibition to activation. The CS-bound HB-GAM promotes neurite growth through binding to the cell surface proteoglycan glypican-2; furthermore, HB-GAM abrogates the CS ligand binding to the inhibitory receptor PTPs (protein tyrosine phosphatase sigma). Our in vivo studies using two-photon imaging of CNS injuries support the in vitro studies and show that HB-GAM increases dendrite regeneration in the adult cerebral cortex and axonal regeneration in the adult spinal cord. Our findings may enable the development of novel therapies for CNS injuries.Peer reviewe

Transmembrane Prostatic Acid Phosphatase (TMPAP) Interacts with Snapin and Deficient Mice Develop Prostate Adenocarcinoma

Peer reviewe

TMPAP co-localize and interact with snapin in the cell lamellipodia.

<p>A, co-localization (yellow) of TMPAP (green) with snapin (red) was observed in the vesicles and lamellipodia of the TMPAP/LNCaP cells. Arrows mark the co-localization points in the upper panel (scale bar: 20 µm). Lower panel (scale bar: 3 µm) showing the lamellipodia region, amplification of the area marked with a box in the upper panel (left). B, intensification of donor (TMPAP-GFP) fluorescence in LNCaP cells was observed after acceptor (snapin-DsRed) photobleaching which confirms FRET between two molecules (Scale bar: 2 µm).</p

DLP lobeexhibits the primary changes in the PAP^−/− mouse prostate.

<p>The panels show an overview of the 12-old mice prostate dissected lobes. The DLP, AP and VP lobes were dissected from WT and PAP^−/− mouse. The monolayer epithelium (white arrows) is seen in all the lobes of the WT mouse, whereas in the PAP^−/− mouse an increased amount of cells is present in the lumen of the DLP lobe (black arrows). The AP and VP of PAP^−/− mouse show no significant changes. Scale bars: 100 µm.</p

Significant ontological terms obtained with GoMiner software from two-color microarrays experiments.

<p><b>GO ID</b>: gene ontology ID accession number. <b><i>P</i></b><b>-value</b>: <i>P</i>-value for the number of changed genes in the input list, significant <i>P</i>-value <0.05. <b>Term</b>: associated ontological term. <b>Rows in bold</b>: relevant ontological groups for vesicular transport. Mice in microarray experiment per group, <i>n = </i>3.</p