Exocytosis

  • Article
    | Open Access

    Molecular tethers physically bridge transport vesicles to their target membranes as a prerequisite step for fusion. Here the authors control vesicle tethering using optogenetic approaches to study the interplay between vesicle tethering and fusion.

    • Seong J. An
    • , Felix Rivera-Molina
    •  & Derek Toomre
  • Article
    | Open Access

    Cells locally expand and retract their surface in response to environmental factors such as changes in membrane tension. Here the authors show the membrane adapter, dynamin2, locally constricts surface membrane to form an isolated but contiguous membrane reservoir that can open upon phospholipid scrambling via TMEM16F.

    • Christine Deisl
    • , Donald W. Hilgemann
    •  & Michael Fine
  • Article
    | Open Access

    Autosomal dominant polycystic kidney disease is characterized by the formation of cysts in the kidney. Here the authors show that cystic extracellular vesicles/exosomes play a critical role in regulating the biology and function of adjacent cells, including renal epithelial cells, fibroblasts and macrophages, and contribute to renal cyst growth.

    • Hao Ding
    • , Linda Xiaoyan Li
    •  & Xiaogang Li
  • Article
    | Open Access

    Synaptotagmin 1 (Syt1) is the calcium sensor for fast synchronous neurotransmitter release but the mechanism by which it functions is still under debate. Here, the authors combine EPR measurements and functional studies and observe that different faces of the Syt1 C2B domain play different roles in regulating neurotransmitter release and they show that the expansion of the fusion pore is mediated by membrane contact of the C2B arginine apex.

    • Sarah B. Nyenhuis
    • , Nakul Karandikar
    •  & David S. Cafiso
  • Article
    | Open Access

    Action potentials induce synchronous and asynchronous release of neurotransmitters. Here, the authors show that the synchronous and asynchronous release sites are aligned with AMPARs and NMDARs, respectively, in mouse hippocampal synapses. This organization allows efficient activation of NMDARs.

    • Shuo Li
    • , Sumana Raychaudhuri
    •  & Shigeki Watanabe
  • Article
    | Open Access

    Glucagon is elevated Type-2 diabetes, which contributes to poor glucose control in patients with the disease. Here the authors report that secretion of the hormone is controlled by paracrine inhibition, and that resistance of α-cells to somatostatin can explain hyperglucagonemia in type-2 diabetes.

    • Muhmmad Omar-Hmeadi
    • , Per-Eric Lund
    •  & Sebastian Barg
  • Article
    | Open Access

    Endophilins-A are conserved membrane-associated proteins required for endocytosis. Here, the authors report that endophilins-A also promote exocytosis of neurosecretory vesicles by coordinating priming and fusion through intersectin-1, independently of their roles in different types of endocytosis.

    • Sindhuja Gowrisankaran
    • , Sébastien Houy
    •  & Ira Milosevic
  • Article
    | Open Access

    Munc18-1 and Munc13-1 are key for the exquisite regulation of neurotransmitter release. Here biophysical experiments show how αSNAP inhibits liposome fusion mediated by the neuronal SNAREs and how Munc18-1 overcomes this inhibition, ensuring that release depends on Munc18-1 and Munc13-1.

    • Karolina P. Stepien
    • , Eric A. Prinslow
    •  & Josep Rizo
  • Article
    | Open Access

    Plasmodium and Toxoplasma parasites rely on rhoptry exocytosis for invasion, but the underlying mechanism is not known. Here, Suarez et al. characterize rhoptry apical surface proteins (RASP) that localize to the rhoptry cap and bind charged lipids, and are essential for rhoptry secretion and invasion.

    • Catherine Suarez
    • , Gaëlle Lentini
    •  & Maryse Lebrun
  • Article
    | Open Access

    Regulated exocytosis of neuronal synaptic vesicles is substantially faster than that of endocrine dense core vesicles despite similar molecular machineries. Here authors compare SNARE-mediated fusion of purified synaptic vesicles with insulin vesicles and see disparities in calcium-triggered fusion rates.

    • Alex J. B. Kreutzberger
    • , Volker Kiessling
    •  & Lukas K. Tamm
  • Article
    | Open Access

    Many legumes accommodate rhizobial symbionts via transcellular infection threads. Here the authors show that in Medicago root hairs, polar growth of the infection thread requires a tip-localized protein complex consisting of VPY and VPY-like proteins that are stabilized by the E3 ligase LIN, as well as an exocyst complex subunit.

    • Cheng-Wu Liu
    • , Andrew Breakspear
    •  & Jeremy D. Murray
  • Article
    | Open Access

    The mechanisms underlying synaptic heterogeneity of neurotransmission at mature calyx synapses remain unclear. Here, authors identify two morphological modules that have distinct topology of calcium channel clusters and spatial coupling distance to synaptic vesicles, which may account for different release probability and short-term plasticity in calyces with differing morphology.

    • Adam Fekete
    • , Yukihiro Nakamura
    •  & Lu-Yang Wang
  • Article
    | Open Access

    Exocyst complex tethers vesicles to plasma membranes, but assembly mechanisms remain unclear. Here, the authors use Cas9 gene editing to tag exocyst components in epithelial cells, and find that exocyst subcomplexes are recruited to membranes independently, but are both needed for vesicle fusion.

    • Syed Mukhtar Ahmed
    • , Hisayo Nishida-Fukuda
    •  & Ian G. Macara
  • Article
    | Open Access

    Existing pH-sensitive red fluorescent protein probes don’t perform well in monitoring exocytosis and endocytosis. Here, the authors combine organic dyes with self-labeling tags or antibodies to develop semisynthetic protein conjugates that can image synaptic vesicle fusion events in living cells.

    • Magalie Martineau
    • , Agila Somasundaram
    •  & David Perrais
  • Article
    | Open Access

    The exocyst delivers basolateral proteins from the secretory pathway to the plasma membrane of epithelial cells close to tight junctions. Here the authors show that Par3 acts as a docking site for the exocyst to regulate polarized delivery of basolateral proteins and this is essential to prevent apoptosis and promote mammary cell survival.

    • Syed Mukhtar Ahmed
    •  & Ian G. Macara
  • Article
    | Open Access

    Membrane fusion during exocytosis is mediated by interaction between SNARE proteins on vesicles and the cell membrane, but how SNARE complex assembly is initiated remains unknown. Here, the authors show that interaction of Sec3 with Sso2 on the plasma membrane promotes formation of an Sso2–Sec9 complex, an early step in SNARE assembly, likely by inhibiting Sso2 auto-inhibition.

    • Peng Yue
    • , Yubo Zhang
    •  & Wei Guo
  • Article
    | Open Access

    Multivesicular bodies (MVB) are endosomal compartments that can either fuse with the plasma membrane for the secretion of exosomes, or fuse with the lysosome and be degraded along with their contents. Here, the authors show that ISGylation of the MVB protein TSG101 impairs exosome secretion and acts as a regulator of MVB fate.

    • Carolina Villarroya-Beltri
    • , Francesc Baixauli
    •  & Francisco Sánchez-Madrid
  • Article
    | Open Access

    As vesicles fuse to the plasma membrane, they form intermediate Ω-shaped structures followed by either closure of the pore or full merging with the plasma membrane. Here Wen et al. show that dynamic actin assembly provides membrane tension to promote Ω merging in neuroendocrine cells and synapses.

    • Peter J. Wen
    • , Staffan Grenklo
    •  & Ling-Gang Wu
  • Article
    | Open Access

    Chloride intracellular channel (CLIC) 4 is an ion channel, localized in the cytoplasm, and first identified as an actin binding protein. Here, Chou et al.knockout CLIC4 in mice and observe tubulogenesis and renal proximal tubule dilation defects, which is caused by irregular actin and endosomal trafficking.

    • Szu-Yi Chou
    • , Kuo-Shun Hsu
    •  & Ching-Hwa Sung
  • Article
    | Open Access

    The cytoskeleton plays a crucial role in secretion. Here Tran et al.demonstrate that cortical actin is rearranged at the site of vesicle fusion and recruited to fused secretory granules in Drosophila salivary glands, and show that branched actin nucleators are required for cargo expulsion.

    • Duy T. Tran
    • , Andrius Masedunskas
    •  & Kelly G. Ten Hagen
  • Article
    | Open Access

    Synaptic assembly depends on trans-synaptic Neurexin/Neuroligin signalling. Here, Muhammad et al. show that Spinophilin, a pre-synaptic scaffolding protein, interacts with Neurexin, in competition with Syd-1, to regulate the formation and function of synaptic active zones at Drosophilaneuromuscular junctions.

    • Karzan Muhammad
    • , Suneel Reddy-Alla
    •  & Stephan J. Sigrist
  • Article
    | Open Access

    Cell shape is determined by a combination of biochemical regulation and mechanical forces. By imaging the dynamic behaviour of growth regulatory proteins in fission yeast and integrating these data within a mechanical model, Abenza et al. find that exocytosis plays a dominant role in shaping growth domains.

    • Juan F. Abenza
    • , Etienne Couturier
    •  & Rafael E. Carazo Salas
  • Article
    | Open Access

    Neurotransmission is mediated by synaptic vesicles (SVs) fusion with the plasma membrane near active zones. Here, Gimber et al.observe that rapid diffusional spread and confinement is followed by slow reclustering of SV proteins at the periactive endocytic zone through SV protein association with the clathrin-based machinery.

    • Niclas Gimber
    • , Georgi Tadeus
    •  & Volker Haucke
  • Article
    | Open Access

    Synapsins anchor synaptic vesicles (SVs) to the actin cytoskeleton to establish the reserve vesicle pool. Here Tanget al. show that SUMOylation of synapsin 1a enhances its interaction with SVs to promote efficient reclustering following stimulation, and a mutation linked to autism and epilepsy leads to defective SUMOylation.

    • Leo T. -H. Tang
    • , Tim J. Craig
    •  & Jeremy M. Henley
  • Article
    | Open Access

    Synaptic vesicle fusion involves a multi-protein assembly called the SNARE complex that is tightly regulated both spatially and temporally. Here Kavanagh et al. show that after vesicle fusion and SNARE complex disassembly in the synapse, the SNARE protein syntaxin1a is sequestered in a monomeric form by munc18-1, preventing ectopic SNARE complex assembly.

    • Deirdre M. Kavanagh
    • , Annya M. Smyth
    •  & Rory R. Duncan
  • Article |

    Two viral proteins form the nuclear egress complex of herpesviruses, which is essential for the exit of nascent viral capsids from the cell nucleus. Here, the authors use synthetic lipid vesicles to show that the complex can mediate membrane budding in the absence of other cellular factors.

    • Janna M. Bigalke
    • , Thomas Heuser
    •  & Ekaterina E. Heldwein
  • Article
    | Open Access

    Mutations in the fragile X mental retardation protein are implicated in synaptic dysfunction in fragile X syndrome. Here, Ferron et al. show that fragile X mental retardation protein maintains proper neurotransmission by regulating the density of N-type calcium channels in the presynaptic terminal.

    • Laurent Ferron
    • , Manuela Nieto-Rostro
    •  & Annette C. Dolphin
  • Article |

    Rapid synaptic transmission requires efficient recycling of synaptic vesicle membrane proteins. Sochackiet al.use live cell, electron and super-resolution microscopy to visualize exocytosis of vesicular transporters and their rapid recapture in clathrin-rich microdomains in the plasma membrane.

    • Kem A. Sochacki
    • , Ben T. Larson
    •  & Justin W. Taraska
  • Article
    | Open Access

    Exosomes released from cells can transfer RNA to recipient cells. In this study, the authors demonstrate that microRNAs in exosomes from T cells can be transferred to antigen-presenting cells during immune synapsis, and that this can alter gene expression, suggesting a new form of cellular communication.

    • María Mittelbrunn
    • , Cristina Gutiérrez-Vázquez
    •  & Francisco Sánchez-Madrid