Synaptotagmin IX – receptor recycler

The synaptotagmins are a highly conserved family of proteins represented in all tissues. Synaptotagmins expressed in neurons appear to function as Ca²⁺ sensors in synaptic vesicle trafficking. But what are the roles of these proteins in non-neuronal cells? Ronit Sagi-Eisenberg and co-workers have approached this question by studying synaptotagmin IX in rat basophilic leukaemia (RBL) cells (see p. 4307). Combining immunofluorescence analyses with subcellular fractionation, they observe that synaptotagmin IX resides in the pericentriolar endocytic recycling compartment (ERC) – a compartment involved in both recycling of plasma membrane receptors and trafficking between early endosomes and the trans Golgi network. They also find that synaptotagmin IX colocalizes with tubulin at the microtubule-organizing centre. Furthermore, they demonstrate that it coimmunoprecipitates with tubulin from intact cells and that chimeric proteins containing the synaptotagmin IX C2A/C2B domain pull down tubulin from cell lysates. The authors go on to show that antisense synaptotagmin IX RNA slows recycling of transferrin from the ERC to the plasma membrane. They therefore propose that the protein functions as link between vesicles recycling from the ERC to the surface and the microtubule tracks on which they travel.