Golgi inheritance: shaken but not stirred

What is the fate of the mammalian Golgi apparatus during mitosis? This seemingly simple question has become part of the wider debate concerning the nature of the Golgi apparatus and the mechanism of secretory protein transport. At the heart of this debate is the question of whether the Golgi is an organelle with its own separate identity, or a complex transport intermediate containing secretory cargo that is populated by enzymes rapidly recycling to and from the ER (Glick, 2002). In recent years, this debate has been propelled by the use of microscopy techniques that allow fluorescent protein tagged Golgi enzymes to be detected in living cells, and quantitative measurements of their localization, rates of transport between the ER and Golgi, and their diffusion rates in these two compartments to be made (Cole et al., 1996). The initially surprising results from the use of such techniques were that Golgi enzymes showed high diffusional mobility and are recycling between the ER and Golgi, so that at steady state over 30% of 1, 4-galactosyltransferase, a medial/trans-Golgi enzyme, was present in the ER (Cole et al., 1996; Zaal et al., 1999). Meanwhile, other observations showed that imposing a block on the COPII vesicle formation pathway used by cargo molecules exiting the ER by introducing dominant-negative forms of the Sar1 GTPase into cells lead to the redistribution of Golgi enzymes back into the ER (Storrie et al., 1998). This is similar to the phenotype of brefeldin A (BFA)–treated cells, where the Golgi fuses with the ER due to deregulation of the ARF1 GTPase and its associated coat proteins (Lippincott-Schwartz et al., 1989). These findings lead to the proposal that Golgi proteins might accumulate in the ER during mitosis as a result of their normal interphase recycling pathway (Fig. 1), combined with the mitotic block in protein transport between the ER and Golgi (Zaal et al., 1999; Lippincott-Schwartz and Zaal, 2000). Older observations had also suggested that such a pathway might exist in mitotically arrested cells where Golgi enzymes were found in the ER (Thyberg and Moskalewski, 1992). This was an alternative to a previous model (Fig. 1) in which the Golgi was said to directly fragment into many small vesicles and tubular remnants (Lucocq et al., 1987; Shima et al., 1997). Various lines of evidence were provided to support the conclusion that in mitosis Golgi enzymes and lipids were present within a large continuous membrane system, namely the ER, rather than in unconnected fragments derived from the Golgi (Zaal et al., 1999). These findings have now been reinvestigated by two groups taking complementary approaches for determining the fate of the Golgi in mitosis (Axelsson and Warren, 2004; Pecot and Malhotra, 2004).