Deletion of the SNARE vti1b in mice results in loss of a single SNARE partner, syntaxin 8

Vadim Atlashkin, Vera Kreykenbohm, Eeva-Liisa Eskelinen, Dirk Wenzel, Afshin Fayyazi, Gabriele Fischer von Mollard

SNARE proteins participate in recognition and fusion of membranes. A SNARE complex consisting of vti1b, syntaxin 8, syntaxin 7 and endobrevin/VAMP-8 has been identified recently which is required for fusion of late endosomes in vitro. Here, we generated mice deficient for vti1b to study the function of this protein in vivo. Vti1b deficient mice had reduced amounts of syntaxin 8 due to degradation of syntaxin 8 protein while the amounts of syntaxin 7 and endobrevin did not change. These data indicate that vti1b was specifically required for the stability of a single SNARE partner. Vti1b deficient mice were viable and fertile. Most vti1b deficient mice were indistinguishable from wild type mice and did not display defects in transport to the lysosome. However, 20% of the vti1b deficient mice were smaller. Lysosomal degradation of an endocytosed protein was slightly delayed in hepatocytes derived from these mice. Multivesicular bodies and autophagic vacuoles accumulated in hepatocytes of some smaller vti1b deficient mice. This suggests that other SNAREs can compensate for the reduction in syntaxin 8 and for the loss of vti1b in most mice even though vti1b shares only 30% amino acid identity with its closest relative.