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| Open AccessIn situ structure of actin remodeling during glucose-stimulated insulin secretion using cryo-electron tomography
Actin mediates insulin secretion in pancreatic β-cells through remodeling. Here, authors report the in situ structure of actin remodeling and quantify changes in architecture, alignment, and interactions during glucose-stimulated insulin secretion.
- Weimin Li
- , Angdi Li
- & Liping Sun
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Article
| Open AccessA phosphoinositide switch mediates exocyst recruitment to multivesicular endosomes for exosome secretion
The molecular mechanism by which exosomes are released from cells is unclear. Here the authors report that a phosphatidylinositide conversion couples the recruitment of the octameric exocyst complex to multivesicular endosomes for exosome secretion.
- Di-Ao Liu
- , Kai Tao
- & Wei Guo
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Article
| Open AccessMitochondria are secreted in extracellular vesicles when lysosomal function is impaired
Mitochondrial quality control is critical for cellular homeostasis and survival. Here, the authors identify that defective mitochondria can be eliminated via secretion in large extracellular vesicles when internal lysosomal degradation is compromised.
- Wenjing Liang
- , Shakti Sagar
- & Åsa B. Gustafsson
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| Open AccessTetraspanin-8 sequesters syntaxin-2 to control biphasic release propensity of mucin granules
The mechanisms regulating granule secretion are not fully understood. Here the authors show that tetraspanin-8 sequesters syntaxin-2 at the cell surface, limiting the syntaxin available for fusion and the quantities of mucin secreted. This mechanism may also apply to insulin release
- José Wojnacki
- , Agustin Leonardo Lujan
- & Vivek Malhotra
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Article
| Open AccessZinc homeostasis governed by Golgi-resident ZnT family members regulates ERp44-mediated proteostasis at the ER-Golgi interface
Zinc is vital to protein quality control in the early secretory pathway. Here, authors demonstrate distinct roles of the Golgi-resident zinc transporters for the maintenance of zinc homeostasis and the regulation of a zinc-dependent chaperone, ERp44.
- Yuta Amagai
- , Momo Yamada
- & Kenji Inaba
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Article
| Open AccessThe K/HDEL receptor does not recycle but instead acts as a Golgi-gatekeeper
In contrast to the current model based on fast recycling of the K/HDEL receptor (ERD2) between the ER and the Golgi apparatus, here authors show evidence that ERD2 is specifically retained in the Golgi apparatus and evades joining its ligands en route to the ER.
- Jonas C. Alvim
- , Robert M. Bolt
- & Jurgen Denecke
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Article
| Open AccessSpatial proteomics reveals secretory pathway disturbances caused by neuropathy-associated TECPR2
Disease-associated mutations in the protein TECPR2 have so far been mainly studied with respect to autophagy. Using complementary proteomics approaches, the authors identify trafficking and sorting defects along the secretory pathway upon TECPR2 deficiency and provide evidence that TECPR2 associates with the ER-Golgi interface.
- Karsten Nalbach
- , Martina Schifferer
- & Christian Behrends
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| Open AccessDynamic tracking and identification of tissue-specific secretory proteins in the circulation of live mice
The in vivo identification of proteins secreted from a specific cell type or tissue remains challenging. Here, the authors develop a proximity labeling-based method to selectively label secreted proteins and combine it with proteomics to identify liver secretory proteins in mouse plasma.
- Kwang-eun Kim
- , Isaac Park
- & Jae Myoung Suh
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Article
| Open AccesspHmScarlet is a pH-sensitive red fluorescent protein to monitor exocytosis docking and fusion steps
A number of pH-sensitive fluorescent proteins exist which enable monitoring of some but not all steps of exocytosis. Here the authors engineer a bright, photostable red pH-sensitive fluorescent protein, pHmScarlet, to allow visualisation of the docking and fusion events of exocytosis.
- Anyuan Liu
- , Xiaoshuai Huang
- & Pingyong Xu
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Article
| Open AccessPharmacological induction of selective endoplasmic reticulum retention as a strategy for cancer therapy
Inhibition of PERK, an endoplasmic reticulum (ER) unfolded protein response (UPR) protein, is a potential pharmacological target for cancer treatment. Here, the authors show that inhibition of PERK under ER stress affects trafficking from the ER to the surface of several key receptor tyrosine kinases, suggesting a selective ER retention.
- Mohamed Mahameed
- , Shatha Boukeileh
- & Boaz Tirosh
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Article
| Open AccessTDP-43 facilitates milk lipid secretion by post-transcriptional regulation of Btn1a1 and Xdh
Milk lipid secretion is a critical process for the delivery of nutrition and energy from parent to offspring. Here the authors found that TDP-43, a RNA-binding protein, is required for milk lipid secretion by post-transcriptional regulation of Btn1a1 and Xdh mRNA stability.
- Limin Zhao
- , Hao Ke
- & Baowei Jiao
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Article
| Open AccessPituitary cell translation and secretory capacities are enhanced cell autonomously by the transcription factor Creb3l2
Pituitary POMC secreting cells achieve high hormone expression levels after birth but the mechanism for this regulation is unclear. Here, the authors show that this process is driven cell autonomously by the differentiation factor Tpit that activates the bZIP transcription factors Creb3l2 and XBP1 to enhance translation and secretory capacities.
- Konstantin Khetchoumian
- , Aurélio Balsalobre
- & Jacques Drouin
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Article
| Open AccessDopey1-Mon2 complex binds to dual-lipids and recruits kinesin-1 for membrane trafficking
Proteins are transported among eukaryotic organelles along the cytoskeleton in membrane carriers. Here authors find that the Dopey1-Mon2 complex functions as a dual-lipid-regulated cargo-adaptor to recruit kinesin-1 to secretory and endocytic organelles or membrane carriers.
- Divyanshu Mahajan
- , Hieng Chiong Tie
- & Lei Lu
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Article
| Open AccessKIBRA controls exosome secretion via inhibiting the proteasomal degradation of Rab27a
Exosomes are intercellular signaling vesicles created by fusion of multivesicular bodies (MVBs) and the plasma membrane (PM), but secretory regulation is ill-defined. Song et al. show that KIBRA controls exosome secretion by protecting Rab27a from proteasomal degradation, promoting MVB-PM docking.
- Lin Song
- , Shi Tang
- & Yifeng Du
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Article
| Open AccessSulfisoxazole inhibits the secretion of small extracellular vesicles by targeting the endothelin receptor A
Extracellular vesicles are released from cells and permit communication between different cell types. Here, the authors identify that the FDA approved antibiotic sulfisoxazole, can block the release of these vesicles in breast cancer cells resulting in reduced cell growth in vitro and in vivo.
- Eun-Ju Im
- , Chan-Hyeong Lee
- & Moon-Chang Baek
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Article
| Open AccessA TonB-dependent transporter is required for secretion of protease PopC across the bacterial outer membrane
TonB-dependent transporters (TBDTs) are outer membrane proteins that import nutrients and bacteriocins in bacteria. Here, Gómez-Santos et al. show that a TBDT is required for secretion of a protease in Myxococcus xanthus, suggesting that some TBDTs may be involved in protein secretion.
- Nuria Gómez-Santos
- , Timo Glatter
- & Lotte Søgaard-Andersen
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Article
| Open AccessKDEL receptor regulates secretion by lysosome relocation- and autophagy-dependent modulation of lipid-droplet turnover
Inter-organelle signaling coordinates adaptive responses via currently unknown mechanisms. Here, Tapia et al. show that KDEL signaling repositions lysosomes in a complex process termed ‘traffic-induced degradation response for secretion’ (TIDeRS) that connects multiple pathways and Golgi secretion.
- Diego Tapia
- , Tomás Jiménez
- & Jorge Cancino
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Article
| Open AccessLand-locked mammalian Golgi reveals cargo transport between stable cisternae
The different composition of Golgi cisternae gave rise to two different models for intra-Golgi traffic: one where stable cisternae communicate via vesicles and another one where cisternae biochemically mature to ensure anterograde transport. Here, the authors provide evidence in support of the stable compartments model.
- Myun Hwa Dunlop
- , Andreas M. Ernst
- & James E. Rothman
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| Open AccessAn exported protein-interacting complex involved in the trafficking of virulence determinants in Plasmodium-infected erythrocytes
Plasmodium-infected red blood cells export virulence factors, such asPfEMP1, to the cell surface. Here, the authors identify a protein complex termed EPIC that interacts with PfEMP1 during export, and they show that knockdown of an EPIC component affects parasite virulence.
- Steven Batinovic
- , Emma McHugh
- & Leann Tilley
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Article
| Open AccessExosomes maintain cellular homeostasis by excreting harmful DNA from cells
The role of exosomes in intercellular communication is well established, however less in known about the biological roles of exosome secretion in exosome-secreting cells. Here the authors show that exosome secretion controls cellular homeostasis in exosome-secreting cells by removing harmful cytoplasmic DNA from cells.
- Akiko Takahashi
- , Ryo Okada
- & Eiji Hara
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Article
| Open AccessTwo pathways regulate cortical granule translocation to prevent polyspermy in mouse oocytes
Mammalian eggs release cortical granules to avoid being fertilized by more than a single sperm as polyspermy results in nonviable embryos. Here, the authors describe the mechanism driving translocation of the granules to the cortex in the mouse egg and show this process is essential to prevent polyspermy.
- Liam P. Cheeseman
- , Jérôme Boulanger
- & Melina Schuh
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| Open AccessNovel role for anti-Müllerian hormone in the regulation of GnRH neuron excitability and hormone secretion
Anti-Müllerian hormone (AMH) plays a role in sexual differentiation and gonadal function, but extra-gonadal effects of AMH are not known. Here Cimino et al. show that AMH activates a subset of gonadotrophin-releasing hormone (GnRH)-releasing neurons, contributing to luteinizing hormone secretion from the pituitary gland.
- Irene Cimino
- , Filippo Casoni
- & Paolo Giacobini
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| Open AccessSex-specific regulation of follicle-stimulating hormone secretion by synaptotagmin 9
Pituitary gonadotropes secrete follicle-stimulating hormone (FSH) in both male and female mice. Roper et al.show that the synaptotagmin isoform syt-9 is specifically required for FSH secretion, but only in females, revealing a mechanism by which specificity can be encoded in complex secretory cells.
- Lindsey K. Roper
- , Joseph S. Briguglio
- & Edwin R. Chapman
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Article
| Open AccessDirectional cell movement through tissues is controlled by exosome secretion
How cells maintain directional polarity when migrating through a complex environment is not well understood. Here Sung et al. show that autocrine exosome secretion is required for persistent and efficient in vivocancer cell motility and promotes assembly of adhesion complexes by delivering fibronectin-bound exosomes.
- Bong Hwan Sung
- , Tatiana Ketova
- & Alissa M. Weaver
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Mast cells form antibody-dependent degranulatory synapse for dedicated secretion and defence
Mast cells are tissue-resident immune cells important for clearance of parasitic worms but also mediating allergic reactions. Here Joulia et al. show that human mast cells form degranulatory synapses with antibody-targeted cells and pathogens to increase efficiency and minimize off-target effects.
- Régis Joulia
- , Nicolas Gaudenzio
- & Eric Espinosa
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Translocation path of a substrate protein through its Omp85 transporter
The two-partner secretion system transports proteins across the bacterial outer membrane but the molecular mechanisms involved are poorly understood. Here, Baud et al. use site-specific crosslinking to track the path of a protein substrate through the β-barrel of its Omp85 transporter.
- Catherine Baud
- , Jérémy Guérin
- & Françoise Jacob-Dubuisson
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Contact-induced clustering of syntaxin and munc18 docks secretory granules at the exocytosis site
Insulin secretory granules dock at the plasma membrane in a syntaxin-dependent manner prior to exocytosis. Gandasi et al. demonstrate that clusters of syntaxin form de novoat the site of contact, suggesting that such clusters do not act as preformed docking receptor.
- Nikhil R. Gandasi
- & Sebastian Barg
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O-glycosylation modulates integrin and FGF signalling by influencing the secretion of basement membrane components
Altered O-glycosylation of proteins is implicated in various human diseases. In this study, Tian and co-workers study mice that are deficient in the O-glycosylation enzyme Galnt1, and find reduced cell proliferation and organogenesis as well as increased endoplasmic reticulum stress.
- E. Tian
- , Matthew P. Hoffman
- & Kelly G. Ten Hagen
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Malaria parasite tyrosyl-tRNA synthetase secretion triggers pro-inflammatory responses
Parasites such as malaria elicit an immune response in their host, causing cytokine levels to increase. In this study, a parasite housekeeping gene, tyrosyl-tRNA synthetase, is shown to bind to host macrophages and, once inside the cells, enhance the levels of proinflammatory cytokines.
- Tarun Kumar Bhatt
- , Sameena Khan
- & Amit Sharma