Two functions of the p24 complex are described: one connects GPI-anchored proteins to COPII proteins at ER exit sites to facilitate their incorporation into ER-derived vesicles, and the other serves in quality control of GPI-anchored proteins to retrieve unremodeled GPI-anchored proteins from the Golgi back to the ER.

Our results show that COPII coat recruitment by cargo receptors is not constitutive but instead is actively regulated by binding of mature ligands. Therefore, we reveal a novel functional link between luminal cargo maturation and COPII vesicle budding, providing a mechanism to adjust specialized COPII vesicle production to the amount and quality of their luminal cargos that are ready for ER exit. This helps to understand how the ER export machinery adapts to different needs for luminal cargo secretion.

Sikorska et al. find that remodeling of a GPI anchor after its attachment to proteins inside the ER strongly promotes ER export but occurs independently of protein folding, thereby effectively limiting ER quality control, potentially including ER-associated degradation of all GPI-anchored proteins.

SummaryChs3, the catalytic subunit of chitin synthase III in Saccharomyces cerevisiae, is a complex polytopic membrane protein whose plasma membrane expression is tightly controlled: export from the ER requires interaction with Chs7; exit from the Golgi is dependent on the exomer complex, and precise bud neck localization relies on endocytosis. Moreover, Chs3 is efficiently recycled from endosomes to the TGN in an AP-1-dependent manner. Here we show that the export of Chs3 requires the cargo receptor Erv14, in a step that is independent of Chs7. Chs3 oligomerized in the ER through its N-terminal cytosolic region. However, the truncated Δ126Chs3 was still exported by Erv14, but was sent back from the Golgi to the ER in a COPI-and Rer1-dependent manner. A subset of the oligomerization-deficient Chs3 proteins evaded Golgi quality control and reached the plasma membrane, where they were enzymatically active but poorly endocytosed. This resulted in high CSIII levels, but calcofluor white resistance, explained by the reduced intercalation of calcofluor white between nascent chitin fibres. Our data show that the oligomerization of Chs3 through its N-terminus is essential for proper protein trafficking and chitin synthesis and is therefore monitored intracellularly.

No abstract

The nucleolus plays a pivotal role in multiple key cellular processes. An illustrative example is the regulation of mitotic exit in Saccharomyces cerevisiae through the nucleolar sequestration of the Cdc14 phosphatase. The peculiar structure of the nucleolus, however, has also its drawbacks. The repetitive nature of the rDNA gives rise to cohesion-independent linkages whose resolution in budding yeast requires the Cdc14-dependent inhibition of rRNA transcription, which facilitates condensin accessibility to this locus. Thus, the rDNA condenses and segregates later than most other yeast genomic regions. Here, we show that defective function of a small nucleolar ribonucleoprotein particle (snoRNP) assembly factor facilitates condensin accessibility to the rDNA and induces nucleolar hyper-condensation. Interestingly, this increased compaction of the nucleolus interferes with the proper release of Cdc14 from this organelle. This observation provides an explanation for the delayed rDNA condensation in budding yeast, which is necessary to efficiently coordinate timely Cdc14 release and mitotic exit with nucleolar compaction and segregation.

The Cdc14 phosphatase is a key regulator of mitosis in the budding yeast Saccharomyces cerevisiae. Cdc14 was initially described as playing an essential role in the control of cell cycle progression by promoting mitotic exit on the basis of its capacity to counteract the activity of the cyclin-dependent kinase Cdc28/Cdk1. A compiling body of evidence, however, has later demonstrated that this phosphatase plays other multiple roles in the regulation of mitosis at different cell cycle stages. Here, we summarize our current knowledge about the pivotal role of Cdc14 in cell cycle control, with a special focus in the most recently uncovered functions of the phosphatase.

Background: Yeast is a model system for the study of mechanisms governing eukaryotic Golgi-Mn 2ϩ homeostasis. Results: We provide evidence that calcium stimulates ER and late endosome/trans-to cis-Golgi manganese delivery and bypasses the need for Pmr1. Conclusion: Vesicle trafficking promotes organelle-specific ion interchange and cytoplasmic metal detoxification. Significance: Our findings open new perspectives on chemical modifiers of Hailey-Hailey disease.