According to current models of peroxisomal biogenesis, Pex5p cycles between the cytosol and the peroxisome transporting newly synthesized proteins to the organelle matrix. However, little is known regarding the mechanism of this pathway. Here, we show that Pex5p enters and exits the peroxisomal compartment in a process that requires ATP. Insertion of Pex5p into the peroxisomal membrane is blocked by anti-Pex14p IgGs. At the peroxisomal level, two Pex14p-associated populations of Pex5p could be resolved, stage 2 and stage 3 Pex5p, both exposing the majority of their masses into the organelle lumen. Stage 3 Pex5p can be easily detected only under ATP-limiting conditions; in the presence of ATP it leaves the peroxisomal compartment rapidly. Our data suggest that translocation of PTS1-containing proteins across the peroxisomal membrane occurs concomitantly with formation of the Pex5p-Pex14p membrane complex and that this is probably the site from which Pex5p leaves the peroxisomal compartment.
TRPV1 receptors expressed by human urothelial cells respond to capsaicin and thermal stimuli. Capsaicin evoked release of adenosine triphosphate suggests that human urothelial TRPV1 is involved in the afferent branch of the micturition reflex. Inflammatory mediators decrease the TRPV1 thermal threshold of activation to body temperature and increase its expression. This finding may be relevant for symptoms associated with cystitis.
DRG11 is a paired domain transcription factor that is necessary for the assembly of the nociceptive circuitry in the spinal cord dorsal horn. It is expressed in small dorsal root ganglion (DRG) neurons and in their projection area in the spinal cord. Drg11 knockout mice exhibit structural and neurochemical defects both at the DRG and spinal superficial dorsal horn and present reduced nociceptive responses. In this study, a polyclonal antibody against DRG11 was generated and used for a detailed systematic spatiotemporal analysis of DRG11 expression during development. DRG11 is first detected at E10.5 in the spinal dorsal horn, DRG and trigeminal ganglion, where it persists until P14-21. At the cranial level, DRG11 expression is observed from E10.5 up to the same early post-natal ages in several cranial sensory ganglia and brain nuclei. These results suggest that DRG11 is required for the establishment of the first neuronal sensory relay along development. Developmental Dynamics 236:2653-2660, 2007.
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