PDZ domains are involved in the scaffolding and assembly of multi-protein complexes at various subcellular sites. We describe here the isolation and characterization of a novel PDZ domain-containing protein that localizes to the Golgi apparatus. Using an in silico cloning approach, we have identified and isolated a cDNA encoding a ubiquitously expressed 59-kDa protein that we call FIG. It is composed of two coiled coil regions, a leucine zipper, and a single PDZ domain. Cytological studies using indirect immunofluorescence microscopy revealed that FIG is a peripheral protein that uses one of its coiled coil domains to localize to the Golgi apparatus. To ascertain the modalities of this Golgi localization, the same coiled coil region was tested for its ability to interact with a panel of coiled coil domain-containing integral membrane Golgi proteins. Using a series of GST fusion protein binding assays, co-immunofluorescence and co-immunoprecipitation experiments, we show that The Golgi apparatus is an intricate, compartmentalized and polarized organelle with two fundamental roles. The first of these is the modification of newly synthesized lipids and proteins as they progress through the organelle, and the second role is to serve as a core hub in the secretory pathway, with proteins and lipids being selectively targeted to several different organelles. These functions require a transport machinery that is driven by a plethora of intricate protein-protein and protein-lipid interactions (for a review, see Ref. 1). Membrane-vesicle recognition and fusion is therefore at the heart of Golgi function.Over the past few years, models of the mechanisms that drive the merging of two phospholipid membranes together have been suggested (for recent reviews, see Refs. 2 and 3). Membrane fusion is now being depicted as a multi-step process that requires the presence and activities of soluble NSF attachment protein receptor (SNARE) 1 proteins. Although their precise role remains somewhat disputed, recent studies indicate that SNARE complexes represent the core machinery for intracellular membrane fusion (for reviews on SNAREs functions, see Refs. 4 -7).Syntaxin 6 is a member of the syntaxin family of SNAREs. To date, this family is comprised of at least 17 members, all of which localize to specific membrane compartments along the endocytic and exocytic pathways (see Refs. 3 and 4). Syntaxin 6 has been shown by electron microscopy to localize mostly to the trans-Golgi network (TGN) and, to a lesser extent, to the Golgi stack (8 -12). Although the primary role of syntaxin 6 remains elusive, it is known to interact with the Rab5 effector EEA1 (early endosomal autoantigen) protein (13). This interaction with EEA1 (early endosomal autoantigen) suggests that syntaxin 6 may function in tethering of post-Golgi vesicles to early endosomes, which raises the possibility that it may regulate early endosome fusion (13). Knowing the interacting partners of syntaxin 6 is an important step toward a better understanding of its function and may s...

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Activating oncogenic mutations of receptor tyrosine kinases (RTKs) have been reported in several types of cancers. In many cases, genomic rearrangements lead to the fusion of unrelated genes to the DNA coding for the kinase domain of RTKs. All RTK-derived fusion proteins reported so far display oligomerization sequences within the 5 fusion partners that are responsible for oncogenic activation. Here, we report a mechanism by which an altered RTK gains oncogenic potential in a glioblastoma cell line. A microdeletion on 6q21 results in the fusion of FIG, a gene coding