Organisation of human ER-exit sites: requirements for the localisation of Sec16 to transitional ER

Hughes, Helen; Budnik, Annika; Schmidt, Katy; Palmer, Krysten J.; Mantell, Judith; Noakes, Chris; Johnson, Andrew; Carter, Deborah A.; Verkade, Paul; Watson, Peter; Stephens, David

doi:10.1242/jcs.044032

Cited by 139 publications

(200 citation statements)

References 42 publications

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“…However, it does not preclude mitotic inhibition of interactions of Sec16 with downstream COPII components (AltanBonnet et al, 2006). Although the mechanisms underlying this inhibition remain unknown, these data also reinforce previous data showing that Sar1, Sec23-Sec24, Sec13-Sec31 all lie downstream of Sec16 (Ivan et al, 2008;Hughes et al, 2009). In fixed cells expressing Venus-Sec16AN, other COPII proteins, Sec24C ( Fig.…”

Section: Resultssupporting

confidence: 89%

“…Lentiviral transduction of FP-Sec16A was precluded by persistent recombination of the parent vector during cloning. Importantly, Venus-Sec16AN includes both the central conserved domain and upstream sequences shown to be necessary for membrane association and targeting to ERES (Ivan et al, 2008;Hughes et al, 2009). Specifically, it colocalises exactly with endogenous Sec16A and localises adjacent to Sec24C and Sec31A labelling, as is seen for endogenous Sec16A ); its expression does not alter the expression of endogenous Sec16A, and it rescues the phenotypes of decreased ERES number and Golgi fragmentation caused by suppression of endogenous Sec16A (supplementary material Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Together, these components form a vesicle coat that selects cargo for export, deforms the membrane, and ultimately generates coated transport vesicles following budding. An additional component, Sec16, potentiates budding (Supek et al, 2002) and appears to mark the transitional ER membrane and define the site of COPII vesicle budding (Connerly et al, 2005;Ivan et al, 2008;Hughes et al, 2009). Inhibition of vesicle budding from the ER during prometaphase (Farmaki et al, 1999) correlates with the loss of COPII proteins (Sec23-Sec24 and Sec13-31) from the ERES membrane (Farmaki et al, 1999;Hammond and Glick, 2000;Prescott et al, 2001;Stephens, 2003;Altan-Bonnet et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

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Sec16A defines the site for vesicle budding from the endoplasmic reticulum on exit from mitosis

Hughes

Stephens

2010

Journal of Cell Science

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SummaryMitotic inhibition of COPII-dependent export of proteins from the endoplasmic reticulum results in disassembly of the Golgi complex. This ensures ordered inheritance of organelles by the two daughter cells. Reassembly of the Golgi is intimately linked to the reinitiation of ER export on exit from mitosis. Here, we show that unlike all other COPII components, which are cytosolic during metaphase, Sec16A remains associated with ER exit sites throughout mitosis, and thereby could provide a template for the rapid assembly of functional export domains in anaphase. Full assembly of COPII at exit sites precedes reassembly of the Golgi in telophase.

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Section: Resultssupporting

confidence: 89%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Sec16A defines the site for vesicle budding from the endoplasmic reticulum on exit from mitosis

Hughes

Stephens

2010

Journal of Cell Science

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“…This reflected rapid ER exit dynamics, determined to be on the scale of seconds (Wilhelmi et al, 2016;Antonny et al, 2001;Forster et al, 2006;Sato and Nakano, 2005). There was also a small fraction of SEC16 (14%) adjacent to mature COPII structures (Hughes et al, 2009). Interestingly, overexpressing SAR1 T39N led to the dispersion of Wls throughout the cells and away from SEC16-positive exit sites.…”

Section: Export Of Wls Into Copii Vesicles Depends On Sar1 Activitymentioning

confidence: 98%

A Wntless–SEC12 complex on the ER membrane regulates early Wnt secretory vesicle assembly and mature ligand export

Sun

Zhang

et al. 2017

Journal of Cell Science

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Wntless (Wls) transports Wnt molecules for secretion; however, the cellular mechanism underlying the initial assembly of Wnt secretory vesicles is still not fully defined. Here, we performed proteomic and mutagenic analyses of mammalian Wls, and report a mechanism for formation of early Wnt secretory vesicles on ER membrane. Wls forms a complex with SEC12 (also known as PREB), an ER membrane-localized guanine nucleotide-exchange factor (GEF) activator of the SAR1 (the SAR1A isoform) small GTPase. Compared to palmitoylation-deficient Wnt molecules, binding of mature Wnt to Wls increases Wls-SEC12 interaction and promotes association of Wls with SAR1, the key activator of the COPII machinery. Incorporation of Wls into this exporting ER compartment is affected by Wnt ligand binding and SEC12 binding to Wls, as well as the structural integrity and, potentially, the folding of the cytosolic tail of Wls. In contrast, Wls-SEC12 binding is stable, with the interacting interface biochemically mapped to cytosolic segments of individual proteins. Mutant Wls that fails to communicate with the COPII machinery cannot effectively support Wnt secretion. These data suggest that formation of early Wnt secretory vesicles is carefully regulated to ensure proper export of functional ligands.

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“…Recently, it was shown that monoubiquitinylation of Sec31 might regulate coats and would enable the formation of giant-sized COPII cages (Jin et al 2012). It should be noted that another architectural factor, Sec16, is also found at ER exit sites (ERESs) (Connerly et al 2005;Hughes et al 2009). Sec16 can interact with all COPII components; for example, contact with Sec13 is mediated by an ACE1 domain just as is seen in the interaction between Sec13 and Sec31 (Whittle and Schwartz 2010).…”

Section: The Cage Structures Of Vesicle Coatsmentioning

confidence: 99%

Functional Insights from Studies on the Structure of the Nuclear Pore and Coat Protein Complexes

Schwartz

2013

Cold Spring Harbor Perspectives in Biology

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The nuclear envelope (NE) is a specific extension of the endoplasmic reticulum (ER) that wraps around the nucleus and enables the spatial separation of gene transcription and protein translation, one of the signature features of eukaryotes. Rather than being completely closed, the double lipid bilayer of the NE is perforated at sites where the inner and outer nuclear membranes fuse, resulting in circular openings lined with sharply bent membranes. These openings are filled with nuclear pore complexes (NPCs), enormous protein assemblies that facilitate nuclear transport. The scaffold components of the NPC surprisingly share interesting similarities with elements of coat protein complexes, which have general implications for function and evolution of these membrane-coating complexes. Here I discuss, from a structural perspective, what these findings might teach us.A s discussed in other articles, the endoplasmic reticulum (ER) is a structurally and functionally diverse organelle. The nuclear envelope (NE) is perhaps the most extreme substructure of the ER. It consists of two flat nuclear membrane sheets that are kept apart in a well-defined distance of 5 nm and that encapsulate the genetic material of the eukaryotic cell (Stewart et al. 2007;Mekhail and Moazed 2010 Grossman et al. 2012). In electron micrographs, NPCs appear as hollow cylinders with distinct cytoplasmic and nucleoplasmic faces, and have an overall eightfold rotational symmetry (Goldberg and Allen 1996). The best-resolved NPC images are obtained by cryoelectron tomography (cryo-ET), reaching a resolution of up to 6 nm ( Fig. 1) (Beck et al. 2004(Beck et al. , 2007Maimon et al. 2012). In cryo-ET, various building blocks of the NPC can be distinguished, yet individual proteins are not resolved. On the cytoplasmic side of the pore, fiber-like extensions emanate from the central NPC mass.On the nucleoplasmic side, eight filaments protrude and cojoin in a narrow ring, a component named a "fishtrap" or "basket." The central Figure 1. The nuclear pore complex. (A) Cryo-electron tomographic reconstruction of the NPC from Dictyostelium discoideum at 6-nm resolution. Cutaway view across the nuclear envelope (NE). The NPC appears organized into three stacked rings that cover the circular openings in the NE. NPCs show eightfold rotational ring symmetry. On the nucleoplasmic side, eight filaments protrude and cojoin in a ring. This resolution reveals the overall dimensions of the NPC and its most prominent features (labeled). (B) Nucleoporins are organized into subcomplexes that are well conserved across divergent eukaryotes. The main NPC scaffold is likely made up of two heteromeric subassemblies, the Y-complex (dark blue) and the Nic96 or Nup93 complex (light blue). The components of these subassemblies have architectural domains, mainly composed of a-helical stack domains and b-propellers. These scaffold complexes are connected to the pore membrane via membrane proteins (yellow). The other subassemblies of the NPC decorate the main scaffold and perform the m...

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Organisation of human ER-exit sites: requirements for the localisation of Sec16 to transitional ER

Cited by 139 publications

References 42 publications

Sec16A defines the site for vesicle budding from the endoplasmic reticulum on exit from mitosis

Sec16A defines the site for vesicle budding from the endoplasmic reticulum on exit from mitosis

A Wntless–SEC12 complex on the ER membrane regulates early Wnt secretory vesicle assembly and mature ligand export

Functional Insights from Studies on the Structure of the Nuclear Pore and Coat Protein Complexes

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