Syntaxin 13 is a developmentally regulated SNARE involved in neurite outgrowth and endosomal trafficking

In addition to its role in exocytosis, SNAP-25 is essential for axonal outg rowth. In order to identify SNARE proteins involved in neurite growth we ha ve used SNAP-25 antibodies to affinity-purify protein complexes enriched in developing rat brain membrane extracts. We have identified a complex betwe en SNAP-25 and syntaxin 13 predominantly present in brain at embryonic or e arly postnatal stages. We show that syntaxin 13 is developmentally regulate d with a decrease in adult brain. In differentiated neuroendocrine PC12 cel ls as well as primary cortical neurons the protein is localized to a puncta ted and tubular staining in the perinuclear region and along processes with high levels in the central region of growth cones. Carboxy-terminally tagg ed syntaxin 13 was also detected on the plasma membrane by in vivo surface- labelling where it colocalized with SNAP-25. Syntaxin 13 has recently been shown to be implicated in early endosomal trafficking. In our study, coloca lization with internalized transferrin in the cell body and along neurites confirmed endosomal location in both compartments. Finally, overexpression of full-length syntaxin 13 enhanced neurite outgrowth in NGF-stimulated PC1 2 cells, whilst it had no effect on regulated secretion. The data suggest t hat a syntaxin 13-dependent endocytic trafficking step plays a limiting rol e in membrane expansion during neuronal development.