Rizzo et al. demonstrate that Golgi-resident enzymes recycle backwards to promote the maturation of cargo-containing Golgi cisternae.
In mammalian cells, the Golgi apparatus consists of stacks of flat, membrane-bound compartments called cisternae. How secretory proteins move through the stack—from the cis side near the ER to the trans side where they are sorted to their final destination—is unclear. In one model, secretory cargo is transported in vesicles from one cisterna to the next, with each Golgi compartment stably maintaining its own composition. An alternative view is that secretory proteins remain in place while the composition of the cisterna changes around them; Golgi resident enzymes are recycled back to earlier cisternae so that each compartment gradually matures and acquires the composition of the trans-Golgi.
To distinguish between these possibilities, Rizzo et al. generated a version of the cis-/medial Golgi enzyme mannosidase I (MANI) that could reversibly polymerize into a large network incapable of being incorporated into recycling vesicles or tubules. Just like the endogenous enzyme, monomeric MANI localized in cis and medial cisternae and in transport vesicles and tubules around the Golgi stack. But when MANI polymerized, it shifted to the trans-Golgi and was no longer found inside vesicles and tubules. Disrupting the MANI network prompted the enzyme’s incorporation into vesicles and its rapid return to the cis-/medial Golgi.
This suggests that MANI and other Golgi enzymes maintain their localization by recycling backwards as individual cisternae carrying protein cargo mature. Senior author Alberto Luini says that other intra-Golgi transport mechanisms may exist and that some secretory proteins may move forwards through the Golgi in transport vesicles. He now wants to investigate how Golgi enzymes are recycled back to earlier compartments.
Text by Ben Short