Abstract: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… Show more
“…We therefore investigated this using SBP-EGFP-GluK2 in neurons. SBP-EGFP-GluK2 colocalizes with mRuby-Sec23A-labeled ERESs (Budnik and Stephens, 2009, Hughes and Stephens, 2010) in dendrites after biotin-induced release (Figures 2B and 2C; Figure S2A; Movie S2). Figure 2KARs Use Local Secretory Pathway Systems(A) Schematic of dendritic local secretory pathways in neurons, focusing on ER exit sites.(B) Representative fixed confocal images of dendritic ERESs (using the marker mRuby-Sec23a) and SBP-EGFP-GluK2 10 min after biotin addition.…”
SummaryIonotropic glutamate receptor (iGluR) trafficking and function underpin excitatory synaptic transmission and plasticity and shape neuronal networks. It is well established that the transcription, translation, and endocytosis/recycling of iGluRs are all regulated by neuronal activity, but much less is known about the activity dependence of iGluR transport through the secretory pathway. Here, we use the kainate receptor subunit GluK2 as a model iGluR cargo to show that the assembly, early secretory pathway trafficking, and surface delivery of iGluRs are all controlled by neuronal activity. We show that the delivery of de novo kainate receptors is differentially regulated by modulation of GluK2 Q/R editing, PKC phosphorylation, and PDZ ligand interactions. These findings reveal that, in addition to short-term regulation of iGluRs by recycling/endocytosis and long-term modulation by altered transcription/translation, the trafficking of iGluRs through the secretory pathway is under tight activity-dependent control to determine the numbers and properties of surface-expressed iGluRs.
“…We therefore investigated this using SBP-EGFP-GluK2 in neurons. SBP-EGFP-GluK2 colocalizes with mRuby-Sec23A-labeled ERESs (Budnik and Stephens, 2009, Hughes and Stephens, 2010) in dendrites after biotin-induced release (Figures 2B and 2C; Figure S2A; Movie S2). Figure 2KARs Use Local Secretory Pathway Systems(A) Schematic of dendritic local secretory pathways in neurons, focusing on ER exit sites.(B) Representative fixed confocal images of dendritic ERESs (using the marker mRuby-Sec23a) and SBP-EGFP-GluK2 10 min after biotin addition.…”
SummaryIonotropic glutamate receptor (iGluR) trafficking and function underpin excitatory synaptic transmission and plasticity and shape neuronal networks. It is well established that the transcription, translation, and endocytosis/recycling of iGluRs are all regulated by neuronal activity, but much less is known about the activity dependence of iGluR transport through the secretory pathway. Here, we use the kainate receptor subunit GluK2 as a model iGluR cargo to show that the assembly, early secretory pathway trafficking, and surface delivery of iGluRs are all controlled by neuronal activity. We show that the delivery of de novo kainate receptors is differentially regulated by modulation of GluK2 Q/R editing, PKC phosphorylation, and PDZ ligand interactions. These findings reveal that, in addition to short-term regulation of iGluRs by recycling/endocytosis and long-term modulation by altered transcription/translation, the trafficking of iGluRs through the secretory pathway is under tight activity-dependent control to determine the numbers and properties of surface-expressed iGluRs.
“…Moreover, the ERGIC-53/p58 cargo receptor showed decreased Sec13 association at the ERES during mitosis 19, indicating that a reduced ability to assemble the COPII coats at the ERES in mitosis contributed to cargo retention at the RER. Interestingly, Sec16A remains associated with the RER membranes during mitosis, possibly at the ERES 54. It was proposed that this enables a quick reassembly of ERES at the end of mitosis to restore the secretory pathway.…”
Section: Protein Trafficking Is Down-regulated During Mitosismentioning
The secretory pathway delivers proteins synthesized at the rough endoplasmic reticulum (RER) to various subcellular locations via the Golgi apparatus. Currently, efforts are focused on understanding the molecular machineries driving individual processes at the RER and Golgi that package, modify and transport proteins. However, studies are routinely performed using non-dividing cells. This obscures the critical issue of how the secretory pathway is affected by cell division. Indeed, several studies have indicated that protein trafficking is down-regulated during mitosis. Moreover, the RER and Golgi apparatus exhibit gross reorganization in mitosis. Here I provide a relatively neglected perspective of how the mitotic cyclin-dependent kinase (CDK1) could regulate various stages of the secretory pathway. I highlight several aspects of the mitotic control of protein trafficking that remain unresolved and suggest that further studies on how the mitotic CDK1 influences the secretory pathway are necessary to obtain a deeper understanding of protein transport.
“…How COPII coat proteins are localized to discrete ERESs is the focus of intensive studies, and evidence in yeast (Pichia pastoris, Connerly et al, 2005; Saccharomyces cerevisiae, Shindiapina and Barlowe, 2010) and metazoans (Watson et al, 2006;Bhattacharyya and Glick, 2007;Hughes et al, 2009;Hughes and Stephens, 2010) supports a crucial role for Sec16. Sec16 depletion in yeast (P. pastoris, Connerly et al, 2005; S. cerevisiae, Castillon et al, 2009) and animal cells (Homo sapiens, Watson et al, 2006;Bhattacharyya and Glick, 2007;Drosophila melanogaster, Ivan et al, 2008) has been linked to disruption of COPII assembly at ERESs, implying that Sec16 is important in COPII-dependent ER export.…”
Section: Introductionmentioning
confidence: 99%
“…This would support the intriguing possibility that ERESs from which COPII carriers are formed are not associated with an ER domain interfacing mobile Golgi stacks. Given that Sec16 functions upstream of COPII components in D. melanogaster (Ivan et al, 2008) and H. sapiens (Hughes and Stephens, 2010), analysis of plant SEC16 would provide insight into ERES domains and the relationship between ERESs and Golgi bodies. With the exception of Sec16, COPII proteins are largely conserved at the sequence level, with plant and metazoan isoforms often outnumbering those of S. cerevisiae (Robinson et al, 2007).…”
Plant cells face unique challenges to efficiently export cargo from the endoplasmic reticulum (ER) to mobile Golgi stacks. Coat protein complex II (COPII) components, which include two heterodimers of Secretory23/24 (Sec23/24) and Sec13/31, facilitate selective cargo export from the ER; however, little is known about the mechanisms that regulate their recruitment to the ER membrane, especially in plants. Here, we report a protein transport mutant of Arabidopsis thaliana, named maigo5 (mag5), which abnormally accumulates precursor forms of storage proteins in seeds. mag5-1 has a deletion in the putative ortholog of the Saccharomyces cerevisiae and Homo sapiens Sec16, which encodes a critical component of ER exit sites (ERESs). mag mutants developed abnormal structures (MAG bodies) within the ER and exhibited compromised ER export. A functional MAG5/SEC16A-green fluorescent protein fusion localized at Golgi-associated cup-shaped ERESs and cycled on and off these sites at a slower rate than the COPII coat. MAG5/SEC16A interacted with SEC13 and SEC31; however, in the absence of MAG5/SEC16A, recruitment of the COPII coat to ERESs was accelerated. Our results identify a key component of ER export in plants by demonstrating that MAG5/SEC16A is required for protein export at ERESs that are associated with mobile Golgi stacks, where it regulates COPII coat turnover.
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