The organization of endoplasmic reticulum export complexes

While the formation of ER to Golgi carrier vesicles in secretory tissues is largely confined to the transitional region facing the juxtanuclear Golgi apparatus (Palade, 1975) , studies in other cell lines have shown that export from the ER can originate from multiple sites that appear randomly distributed throughout the cytoplasm and, in most instances, distant from the Golgi complex. The relationship of these peripheral sites to the transitional region found in secretory cells is unknown, although they are now recognized to consist of clusters of small vesicles and tubular elements (Saraste and Kuismanen, 1984; Schweizer et al., 1990; Saraste and Svensson, 1991; Lotti et al., 1992) re-ferred to as vesicular tubular clusters (VTCs) 1 . While VTCs are readily detectable at 37°C in vivo (Saraste and Kuismanen, 1984; Saraste and Svensson, 1991) and at 32°C in vitro (Plutner et al., 1992; Pind et al., 1994a) , visualization of these structures can be markedly enhanced by incubation of cells at reduced temperature (15°-16°C) (Saraste and Kuismanen, 1984) , presumably due to a rate-limiting step in membrane flow through these intermediates. Elements of VTCs lack luminal continuity with the ER (Saraste and Svensson, 1991; Balch et al., 1994; Connolly et al., 1994) , although tubular extensions of ER into these structures have been observed (Stinchcombe et al., 1995) , particularly in cells infected with certain viruses (Tooze et al., 1984; Krijnse-Locker et al., 1994) , reinforcing their close relationship to ER export.