Lack of the endosomal SNAREs vti1a and vti1b led to significant impairments in neuronal development

Fusion between membranes is mediated by specific SNARE complexes. Here we report that fibroblasts survive the absence of the trans-Golgi network/early endosomal SNARE vti1a and the late endosomal SNARE vti1b with intact organelle morphology and minor trafficking defects. Because vti1a and vti1b are the only members of their SNARE subclass and the yeast homolog Vti1p is essential for cell survival, these data suggest that more distantly related SNAREs acquired the ability to function in endosomal traffic during evolution. However, absence of vti1a and vti1b resulted in perinatal lethality. Major axon tracts were missing, reduced in size, or misrouted in Vti1a−/− Vti1b−/− embryos. Progressive neurodegeneration was observed in most Vti1a−/− Vti1b−/− peripheral ganglia. Neurons were reduced by more than 95% in Vti1a−/− Vti1b−/− dorsal root and geniculate ganglia at embryonic day 18.5. These data suggest that special demands for endosomal membrane traffic could not be met in Vti1a−/− Vti1b−/− neurons. Vti1a−/− and Vti1b−/− single deficient mice were viable without these neuronal defects, indicating that they can substitute for each other in these processes.

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