Secretory traffic triggers the formation of tubular continuities across Golgi sub-compartments

Abstract

The organization of secretory traffic remains unclear, mainly because of the complex structure and dynamics of the secretory pathway. We have thus studied a simplified system, a single synchronized traffic wave crossing an individual Golgi stack, using electron tomography. Endoplasmic-reticulum-to-Golgi carriers join the stack by fusing with cis cisternae and induce the formation of intercisternal tubules, through which they redistribute their contents throughout the stack. These tubules seem to be pervious to Golgi enzymes, whereas Golgi vesicles are depleted of both enzymes and cargo. Cargo then traverses the stack without leaving the cisternal lumen. When cargo exits the stack, intercisternal connections disappear. These findings provide a new view of secretory traffic that includes dynamic intercompartment continuities as key players.

How the Golgi works: A cisternal progenitor model

“…It is important to note that two stacks are not needed to accomplish such transport: because even ministack cisternae are discontinuous, such a fusion event could occur between cisternae within a ministack. In addition, this class of fusion may explain the tubules that have been detected in some laboratories to connect Golgi cisternae (4,5,30).…”

“…Indeed, several thousand vesicles, some of which carry proteins back to the endoplasmic reticulum, surround the Golgi. Membrane tubules have also been detected between Golgi cisternae, under conditions of active secretion (4,5); this scenario would permit cargo movement from one side of the stack to the next, without maturation or vesicle transfer.…”

Mutations in a Highly Conserved Region of the Arf1p ActivatorGEA2Block Anterograde Golgi Transport but Not COPI Recruitment to Membranes

“…There is evidence in both yeast and mammalian cells that COPI mediates the retrograde trafficking of glycosylation enzymes, cargo receptors, and fusion machinery (Nakano, 2004). The precise mechanism of this retrograde trafficking is a subject of ongoing research, and there is debate as to whether retrograde-directed glycosylation enzymes in mammalian cells are packaged into COPI vesicles or are sorted into tubules that connect Golgi cisternae (Kweon et al, 2004;Trucco et al, 2004). Trucco et al (2004) have proposed that COPI vesicles contain not Golgi enzymes but primarily the fusion machinery, such as the SNARE protein membrin.…”

“…The precise mechanism of this retrograde trafficking is a subject of ongoing research, and there is debate as to whether retrograde-directed glycosylation enzymes in mammalian cells are packaged into COPI vesicles or are sorted into tubules that connect Golgi cisternae (Kweon et al, 2004;Trucco et al, 2004). Trucco et al (2004) have proposed that COPI vesicles contain not Golgi enzymes but primarily the fusion machinery, such as the SNARE protein membrin. Recently, it has been demonstrated biochemically that distinct populations of COPIThis article was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E05-04 -0289) on June 1, 2005. containing membranes can be isolated from cells, suggesting that there are different COPI-mediated retrograde trafficking pathways responsible for transporting different retrograde cargo (Malsam et al, 2005).…”

An escort for GPCRs: implications for regulation of receptor density at the cell surface

“…Each layer of the stack, from cis-Golgi to the trans-Golgi network (TGN) contains glycosyltransferases. ER to Golgi carriers join the Golgi stack by fusing with cis cisternae 26 . The transport mechanisms of cargo and enzymes through the Golgi stack has not been completely elucidated and lead to conflicting models 27 .…”