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The coat protein complex II (COPII) mediates forward trafficking of protein and lipid cargoes from the endoplasmic reticulum. COPII is an ancient and essential pathway in all eukaryotes and COPII dysfunction underlies a range of human diseases. Despite this broad significance, major aspects of COPII trafficking remain incompletely understood. For example, while the biochemical features of COPII vesicle formation are relatively well characterized, much less is known about how the COPII system dynamically adjusts its activity to changing physiologic cues or stresses. Recently, post-transcriptional mechanisms have emerged as a major mode of COPII regulation. Here, we review the current literature on how post-transcriptional events, and especially post-translational modifications, govern the COPII pathway.

Intracellular transport undergoes remodeling upon cell differentiation, which involves cell type-specific regulators. Bone morphogenetic protein 2-inducible kinase (BMP2K) has been potentially implicated in endocytosis and cell differentiation but its molecular functions remained unknown. We discovered that its longer (L) and shorter (S) splicing variants regulate erythroid differentiation in a manner unexplainable by their involvement in AP-2 adaptor phosphorylation and endocytosis. However, both variants interact with SEC16A and could localize to the juxtanuclear secretory compartment. Variant-specific depletion approach showed that BMP2K isoforms constitute a BMP2K-L/S regulatory system that controls the distribution of SEC16A and SEC24B as well as SEC31A abundance at COPII assemblies. Finally, we found L to promote and S to restrict autophagic degradation and erythroid differentiation. Hence, we propose that BMP2K-L and BMP2K-S differentially regulate abundance and distribution of COPII assemblies as well as autophagy, possibly thereby fine-tuning erythroid differentiation., Competing Interests: JC, MK, MM, KK, KJ, MB, AK, KP, MM No competing interests declared, (© 2020, Cendrowski et al.)

Intracellular transport undergoes remodeling upon cell differentiation, which involves cell type-specific regulators. Bone morphogenetic protein 2-inducible kinase (BMP2K) has been potentially implicated in endocytosis and cell differentiation but its molecular functions remained unknown. We discovered that its longer (L) and shorter (S) splicing variants regulate erythroid differentiation in a manner unexplainable by their involvement in AP-2 adaptor phosphorylation and endocytosis. However, both variants interact with SEC16A and could localize to the juxtanuclear secretory compartment. Variant-specific depletion approach showed that BMP2K isoforms constitute a BMP2K-L/S regulatory system that controls the distribution of SEC16A and SEC24B as well as SEC31A abundance at COPII assemblies. Finally, we found L to promote and S to restrict autophagic degradation and erythroid differentiation. Hence, we propose that BMP2K-L and BMP2K-S differentially regulate abundance and distribution of COPII assemblies as well as autophagy, possibly thereby fine-tuning erythroid differentiation.

Autophagy targets cytoplasmic materials for degradation and influences cell health. Organelle contact and trafficking systems provide membranes for autophagosome formation, but how different membrane systems are selected for use during autophagy remains unclear. Here, we report a novel function of the endosomal sorting complex required for transport (ESCRT) in the regulation of endoplasmic reticulum (ER) coat protein complex II (COPII) vesicle formation that influences autophagy. The ESCRT functions in a pathway upstream of Vps13D to influence COPII vesicle transport, ER-Golgi intermediate compartment (ERGIC) assembly, and autophagosome formation. Atg9 functions downstream of the ESCRT to facilitate ERGIC and autophagosome formation. Interestingly, cells lacking either ESCRT or Vps13D functions exhibit dilated ER structures that are similar to cranio-lenticulo-sutural dysplasia patient cells with SEC23A mutations, which encodes a component of COPII vesicles. Our data reveal a novel ESCRT-dependent pathway that influences the ERGIC and autophagosome formation. [Display omitted] • The ESCRT and Vps13D function in a common autophagy pathway • The ESCRT influences ER maturation and COPII trafficking • Vps13D influences COPII trafficking • The ESCRT influences ERGIC and Vps13D availability for Atg9 induction of autophagy The removal of cytoplasmic materials by autophagy is important for cell and organism health. Wang et al. identify a relationship between the endosomal sorting complexes required for transport (ESCRT) and Vps13D in the regulation of endoplasmic reticulum (ER) coat protein complex II (COPII) vesicle formation that influences autophagy. [ABSTRACT FROM AUTHOR]

Viruses are obligate intracellular pathogens that utilize cellular machinery for many aspects of their propagation and effective egress of virus particles from host cells is one important determinant of virus infectivity. Hijacking host cell processes applies in particular to the hepatitis B virus (HBV), as its DNA genome with about 3 kb in size is one of the smallest viral genomes known. HBV is a leading cause of liver disease and still displays one of the most successful pathogens in human populations worldwide. The extremely successful spread of this virus is explained by its efficient transmission strategies and its versatile particle types, including virions, empty envelopes, naked capsids, and others. HBV exploits distinct host trafficking machineries to assemble and release its particle types including nucleocytoplasmic shuttling transport, secretory, and exocytic pathways, the Endosomal Sorting Complexes Required for Transport pathway, and the autophagy pathway. Understanding how HBV uses and subverts host membrane trafficking systems offers the chance of obtaining new mechanistic insights into the regulation and function of this essential cellular processes. It can also help to identify potential targets for antiviral interventions. Here, I will provide an overview of HBV maturation, assembly, and budding, with a focus on recent advances, and will point out areas where questions remain that can benefit from future studies. Unless otherwise indicated, almost all presented knowledge was gained from cell culture‐based, HBV in vitro‐replication and in vitro‐infection systems. [ABSTRACT FROM AUTHOR]

In eukaryotes, the endomembrane system allows for spatiotemporal compartmentation of complicated cellular processes. The plant endomembrane system consists of the endoplasmic reticulum, the Golgi apparatus, the trans‐Golgi network, the multivesicular body and the vacuole. Anterograde traffic from the endoplasmic reticulum to the Golgi apparatus is mediated by coat protein complex II (COPII) vesicles. Autophagy, an evolutionarily conserved catabolic process that turns over cellular materials upon nutrient deprivation or in adverse environments, exploits double‐membrane autophagosomes to recycle unwanted constituents in the lysosome/vacuole. Accumulating evidence reveals novel functions of plant COPII vesicles in autophagy and their regulation by abiotic stresses. Here, we summarize current knowledge about plant COPII vesicles in endomembrane trafficking and then highlight recent findings showing their distinct roles in modulating the autophagic flux and stress responses. [ABSTRACT FROM AUTHOR]

Due to the numerous roles plant vacuoles play in cell homeostasis, detoxification, and protein storage, the trafficking pathways to this organelle have been extensively studied. Recent evidence, however, suggests that our vision of transport to the vacuole is not as simple as previously imagined. Alternative routes have been identified and are being characterized. Intricate interconnections between routes seem to occur in various cases, complicating the interpretation of data. In this review, we aim to summarize the published evidence and link the emerging data with previous findings. We discuss the current state of information on alternative and classical trafficking routes to the plant vacuole. [ABSTRACT FROM AUTHOR]

BMP2K (BMP2 inducible kinase) is a serine-threonine kinase with high amino acid homology to a known endocytic regulator, AAK1, and thus has been suspected to act in endocytosis. In our recent study, we report that BMP2K kinase regulates erythroid maturation in a manner that could not be explained by its involvement in endocytosis. Instead, we discovered that in erythroid cells, its splicing variants (BMP2K-L and BMP2K-S) act in opposing ways to regulate autophagic degradation, an important event in erythroid maturation. We also found that both isoforms could interact with a mammalian counterpart of yeast Sec16, SEC16A, a regulator of COPII vesicle-dependent secretory trafficking. BMP2K-L and -S differentially affect SEC16A levels and distribution, as well as abundance of SEC31A at COPII assemblies (SEC31A load). The regulation of SEC31A load by BMP2K variants concerned assemblies positive for SEC24B, a SEC16A interactor implicated in macroautophagy/autophagy. Hence, we found an unusual mechanism of two splicing variants of a kinase playing opposing roles in autophagy, potentially via differential regulation of SEC16A-dependent COPII assembly. Thereby they constitute a regulatory system, that we call the BMP2K-L/S system, fine-tuning autophagy and modulating erythroid maturation. [ABSTRACT FROM AUTHOR]

Historically, studies of intracellular membrane trafficking have focused on the secretory and endocytic pathways and their major organelles. However, these pathways are also directly implicated in the biogenesis and function of other important intracellular organelles, the best studied of which are peroxisomes and lipid droplets. There is a large recent body of work on these organelles, which have resulted in the introduction of new paradigms regarding the roles of membrane trafficking organelles. In this review, we discuss the roles of membrane trafficking in the life cycle of lipid droplets. This includes the complementary roles of lipid phase separation and proteins in the biogenesis of lipid droplets from endoplasmic reticulum (ER) membranes, and the attachment of mature lipid droplets to membranes by lipidic bridges and by more conventional protein tethers. We also discuss the catabolism of neutral lipids, which in part results from the interaction of lipid droplets with cytosolic molecules, but with important roles for both macroautophagy and microautophagy. Finally, we address their eventual demise, which involves interactions with the autophagocytotic machinery. We pay particular attention to the roles of small GTPases, particularly Rab18, in these processes. [ABSTRACT FROM AUTHOR]