A novel Rab6-interacting domain defines a family of Golgi-targeted coiled-coil proteins

In recent years, a large number of coiled-coil proteins localised to the Go lgi apparatus have been identified using antisera from human patients with a variety of autoimmune conditions [1]. Because of their common method of d iscovery and extensive regions of coiled-coil, they have been classified as a family of proteins, the golgins [1]. This family includes golgin-230/245 /256, golgin-97, GM130/golgin-95, golgin-160/MEA-2/GCP170, giantin/macrogol gin and a related group of proteins possibly splice variants - GCP372 and G CP364 [2-11]. GM130 and giantin have been shown to function in the p115-med iated docking of vesicles with Golgi cisternae [12]. In this process, p115, another coiled-coil protein, is though to bind to giantin on vesicles and to GM130 on cisternae, thus acting as a tether holding the two together [12 ,13]. Apart from giantin and GM130, none of the golgins has yet been assign ed a function in the Golgi apparatus. In order to obtain clues as to the fu nctions of the golgins, the targeting to the Golgi apparatus of two members of this family, golgin-230/245/256 and golgin-97, was investigated. Each o f these proteins was shown to target to the Golgi apparatus through a carbo xyterminal domain containing a conserved tyrosine residue, which was critic al for targeting. The domain preferentially bound to nabs on protein blots, and mutations that abolished Golgi targeting resulted in a loss of this in teraction. Sequence analysis revealed that a family of coiled-coil proteins from mammals, worms and yeast contain this domain at their carboxyl termin i. One of these proteins, yeast Imh1p, has previously been shown to have a tight genetic interaction with Rab6 [14]. On the basis of these data, it is proposed that this family of coiled-coil proteins functions in nabs-regula ted membrane-tethering events.