Mitotic ER Exit Site Disassembly and Reassembly Are Regulated by the Phosphorylation Status of TANGO1

ER exit sites in Drosophila display abundant ER-Golgi vesicles and pearled tubes but no megacarriers

“…However, our characterization shows Drosophila ERES-Golgi units as compact membrane assemblages. Although liquid-liquid phase separation may be crucial for aspects of ERES establishment and function (Maeda et al, 2020;Zhang and Rabouille, 2019), their maintenance may be better explained by limited diffusion imposed by enclosing membranes and classical tethering by proteins like Tango1, Grasp65, golgins, and Rab1.…”

Export Control: Post-transcriptional Regulation of the COPII Trafficking Pathway

“…Moreover, PTMs of TANGO1 have been implicated in modulating its role as an ERES assembler and organizer. Recently, Maeda et al demonstrated that TANGO1 is a substrate of the kinase CK1 and the phosphatase PP1, and that TANGO1 phosphorylation by CK1 reduces its interaction with Sec16, leading to a mitosis-linked dissolution of ERES (Maeda et al, 2020). Another study in Drosophila showed that loss of PGANT4, an O-GalNAc transferase, resulted in TANGO1 cleavage and subsequent loss of secretory granules and apical secretion (Zhang et al, 2014).…”

Unscrambling exit site patterns on the endoplasmic reticulum as a quenched demixing process

“…Sec16 is a peripheral membrane protein that is not only found on ERESs but also on the general ER and in the surrounding cytosol, i.e., the protein cycles between the ER/ ERES and the surrounding cytosol with a typical timescale of 10-15 s (32). Recent reports have also uncovered that Sec16 closely interacts with the transmembrane protein TANGO1 (48), whose dephosphorylated form has been shown to be indispensable for ERES formation, i.e., ERESs were observed to disassemble upon phosphorylating TANGO1 (49).…”

“…Therefore, remnant barriers and complex membrane morphologies may still enter the experimentally determined p(A). And 3) ERES formation does not only invoke a single particle species but relies on the interaction of at least TANGO1 and Sec16 (48,49), with a phosphorylation of TANGO1 leading to the rapid disassembly of the ERESs (49). Moreover, COPII proteins are known to interact with Sec16 (32) and TANGO1 (26).…”