HPC‐1/syntaxin 1A and syntaxin 1B play distinct roles in neuronal survival

Abstract Two types of syntaxin 1 isoforms, HPC ‐1/syntaxin 1A ( STX 1A) and syntaxin 1B ( STX 1B), are thought to have similar functions in exocytosis of synaptic vesicles. STX 1A −/− mice which we generated previously develop normally, possibly because of compensation by STX 1B. We produced STX 1B −/− mice using targeted gene disruption and investigated their phenotypes. STX 1B −/− mice were born alive, but died before postnatal day 14, unlike STX 1A −/− mice. Morphologically, brain development in STX 1B −/− mice was impaired. In hippocampal neuronal culture, the cell viability of STX 1B −/− neurons was lower than that of WT or STX 1A −/− neurons after 9 days. Interestingly, STX 1B −/− neurons survived on WT or STX 1A −/− glial feeder layers as well as WT neurons. However, STX 1B −/− glial feeder layers were less effective at promoting survival of STX 1B −/− neurons. Conditioned medium from WT or STX 1A −/− glial cells had a similar effect on survival, but that from STX 1B −/− did not promote survival. Furthermore, brain‐derived neurotrophic factor ( BDNF ) or neurotrophin‐3 supported survival of STX 1B −/− neurons. BDNF localization in STX 1B −/− glial cells was disrupted, and BDNF secretion from STX 1B −/− glial cells was impaired. These results suggest that STX 1A and STX 1B may play distinct roles in supporting neuronal survival by glia. image Syntaxin 1A (STX1A) and syntaxin 1B (STX1B) are thought to have similar functions as SNARE proteins. However, we found that STX1A and STX1B play distinct roles in neuronal survival using STX1A −/− mice and STX1B −/− mice. STX1B was important for neuronal survival, possibly by regulating the secretion of neurotrophic factors, such as BDNF, from glial cells.