The spectrin family member Syne-1 functions in retrograde transport from Golgi to ER.

To address the function of the Golgi- and nuclear envelope-localized spectrin family member synaptic nuclear envelope protein-1 (Syne-1), we expressed two separate recombinant fragments derived from the central portion of the molecule. Both of these fragments were predicted to act as dominant negative inhibitors of Syne-1 function at the Golgi. One of the fragments was previously shown to bind the Golgi complex. The other fragment was found to form microtubule-associated puncta that sequester endogenous Syne-1. Expression of either fragment resulted in a cell type-specific alteration in the structure of the Golgi complex, which appeared to collapse into a compact juxtanuclear structure in some cell types but not others. These fragments were expressed in cultured cells and their effects on Golgi function were examined. Expression of both dominant negative Syne-1 fragments blocked recycling of the endoplasmic reticulum (ER) resident protein disulfide isomerase (PDI), which accumulated in the Golgi complex. In addition, we found that fragment expression altered the distribution of the KDEL receptor and the COP-I coat protein beta-COP, two proteins known to be involved in regulating the retrograde pathway. We conclude that these results indicate a role for Syne-1 in facilitating retrograde vesicular trafficking from the Golgi to the ER.