1. Radioisotope Laboratory, Kyorin University School of Medicine, , Mitaka, Tokyo, Japan;2. Department of Cell Physiology, Kyorin University School of Medicine, , Mitaka, Tokyo, Japan
Abstract:
Two types of syntaxin 1 isoforms, HPC‐1/syntaxin 1A (STX1A) and syntaxin 1B (STX1B), are thought to have similar functions in exocytosis of synaptic vesicles. STX1A?/? mice which we generated previously develop normally, possibly because of compensation by STX1B. We produced STX1B?/? mice using targeted gene disruption and investigated their phenotypes. STX1B?/? mice were born alive, but died before postnatal day 14, unlike STX1A?/? mice. Morphologically, brain development in STX1B?/? mice was impaired. In hippocampal neuronal culture, the cell viability of STX1B?/? neurons was lower than that of WT or STX1A?/? neurons after 9 days. Interestingly, STX1B?/? neurons survived on WT or STX1A?/? glial feeder layers as well as WT neurons. However, STX1B?/? glial feeder layers were less effective at promoting survival of STX1B?/? neurons. Conditioned medium from WT or STX1A?/? glial cells had a similar effect on survival, but that from STX1B?/? did not promote survival. Furthermore, brain‐derived neurotrophic factor (BDNF) or neurotrophin‐3 supported survival of STX1B?/? neurons. BDNF localization in STX1B?/? glial cells was disrupted, and BDNF secretion from STX1B?/? glial cells was impaired. These results suggest that STX1A and STX1B may play distinct roles in supporting neuronal survival by glia.
