scholarly journals Rab2 directs a stop-loss program

2009 ◽  
Vol 186 (6) ◽  
pp. 769-769
Author(s):  
Ben Short
Keyword(s):  
Small Gtpase ◽  
Dense Core ◽  
Dense Core Vesicle ◽  
Stop Loss

Small GTPase supports dense core vesicle maturation in worm neurons.

scholarly journals The Dense-Core Vesicle Maturation Protein CCCP-1 Binds RAB-2 and Membranes through its C-terminal Domain

2017 ◽  
Author(s):  
Jérôme Cattin-Ortolá ◽  
Irini Topalidou ◽  
Annie Dosey ◽  
Alexey J. Merz ◽  
Michael Ailion
Keyword(s):  
Structure Function ◽  
Function Analysis ◽  
Coiled Coil ◽  
Lipid Binding ◽  
Small Gtpase ◽  
Dense Core ◽  
Binding Motif ◽  
Dense Core Vesicle ◽  
Terminal Domain ◽  
C Terminus

AbstractDense-core vesicles (DCVs) are secretory organelles that store and release modulatory neurotransmitters from neurons and endocrine cells. Recently, the conserved coiled-coil protein CCCP-1 was identified as a component of the DCV biogenesis pathway in the nematode C. elegans. CCCP-1 binds the small GTPase RAB-2 and colocalizes with it at the trans-Golgi. Here we report a structure-function analysis of CCCP-1 to identify domains of the protein important for its localization, binding to RAB-2, and function in DCV biogenesis. We find that the CCCP-1 C-terminal domain (CC3) has multiple activities. CC3 is necessary and sufficient for CCCP-1 localization and for binding to RAB-2, and is required for the function of CCCP-1 in DCV biogenesis. Additionally, CCCP-1 binds membranes directly through its CC3 domain, indicating that CC3 may comprise a previously uncharacterized lipid-binding motif. We conclude that CCCP-1 is a coiled-coil protein that binds an activated Rab and localizes to the Golgi via its C-terminus, properties similar to members of the golgin family of proteins. CCCP-1 also shares biophysical features with golgins; it has an elongated shape and forms oligomers.Synopsis statementCCCP-1 is a coiled-coil protein important for dense-core vesicle (DCV) biogenesis. A structure-function analysis of CCCP-1 shows that its C-terminal domain is required for (1) localization to membrane compartments near the trans-Golgi, (2) binding to activated RAB-2, (3) function in DCV biogenesis, and (4) direct binding to membranes. CCCP-1 has an elongated shape and forms oligomers. These findings suggest that CCCP-1 resembles members of the golgin family of proteins that act as membrane tethers.

scholarly journals Atg16L1, an essential factor for canonical autophagy, participates in hormone secretion from PC12 cells independently of autophagic activity

2012 ◽  
Vol 23 (16) ◽  
pp. 3193-3202 ◽  
Author(s):  
Koutaro Ishibashi ◽  
Takefumi Uemura ◽  
Satoshi Waguri ◽  
Mitsunori Fukuda
Keyword(s):  
Pc12 Cells ◽  
Secretory Pathway ◽  
Biological Activities ◽  
Hormone Secretion ◽  
Cell Types ◽  
Small Gtpase ◽  
Dense Core ◽  
Dense Core Vesicle ◽  
Dense Core Vesicles ◽  
Autophagic Activity

Autophagy is a bulk degradation system in all eukaryotic cells and regulates a variety of biological activities in higher eukaryotes. Recently involvement of autophagy in the regulation of the secretory pathway has also been reported, but the molecular mechanism linking autophagy with the secretory pathway remains largely unknown. Here we show that Atg16L1, an essential protein for canonical autophagy, is localized on hormone-containing dense-core vesicles in neuroendocrine PC12 cells and that knockdown of Atg16L1 causes a dramatic reduction in the level of hormone secretion independently of autophagic activity. We also find that Atg16L1 interacts with the small GTPase Rab33A and that this interaction is required for the dense-core vesicle localization of Atg16L1 in PC12 cells. Our findings indicate that Atg16L1 regulates not only autophagy in all cell types, but also secretion from dense-core vesicles, presumably by acting as a Rab33A effector, in particular cell types.

scholarly journals The EARP Complex and its Interactor EIPR-1 are Required for Cargo Sorting to Dense-Core Vesicles

2016 ◽  
Author(s):  
Irini Topalidou ◽  
Jérôme Cattin-Ortolá ◽  
Andrea L. Pappas ◽  
Kirsten Cooper ◽  
Gennifer E. Merrihew ◽  
...  
Keyword(s):  
Peptide Hormones ◽  
Genetic Screen ◽  
Small Gtpase ◽  
Neuroendocrine Cells ◽  
Dense Core ◽  
Dense Core Vesicle ◽  
Dense Core Vesicles ◽  
Wide Range ◽  
Insulinoma Cells ◽  
Cargo Sorting

AbstractThe dense-core vesicle is a secretory organelle that mediates the regulated release of peptide hormones, growth factors, and biogenic amines. Dense-core vesicles originate from the trans-Golgi of neurons and neuroendocrine cells, but it is unclear how this specialized organelle is formed and acquires its specific cargos. To identify proteins that act in dense-core vesicle biogenesis, we performed a forward genetic screen in Caenorhabditis elegans for mutants defective in dense-core vesicle function. We previously reported the identification of two conserved proteins that interact with the small GTPase RAB-2 to control normal dense-core vesicle cargo-sorting. Here we identify several additional conserved factors important for dense-core vesicle cargo sorting: the WD40 domain protein EIPR-1 and the endosome-associated recycling protein (EARP) complex. By assaying behavior and the trafficking of dense-core vesicle cargos, we show that mutants that lack EIPR-1 or EARP have defects in dense-core vesicle cargo-sorting similar to those of mutants in the RAB-2 pathway. Genetic epistasis data indicate that RAB-2, EIPR-1 and EARP function in a common pathway. In addition, using a proteomic approach in rat insulinoma cells, we show that EIPR-1 physically interacts with the EARP complex. Our data suggest that EIPR-1 is a new component of the EARP complex and that dense-core vesicle cargo sorting depends on the EARP-dependent retrieval of cargo from an endosomal sorting compartment.Author SummaryAnimal cells package and store many important signaling molecules in specialized compartments called dense-core vesicles. Molecules stored in dense-core vesicles include peptide hormones like insulin and small molecule neurotransmitters like dopamine. Defects in the release of these compounds can lead to a wide range of metabolic and mental disorders in humans, including diabetes, depression, and drug addiction. However, it is not well understood how dense-core vesicles are formed in cells and package the appropriate molecules. Here we use a genetic screen in the microscopic worm C. elegans to identify proteins that are important for early steps in the generation of dense-core vesicles, such as packaging the correct molecular cargos in the vesicles. We identify several factors that are conserved between worms and humans and point to a new role for a protein complex that had previously been shown to be important for controlling trafficking in other cellular compartments. The identification of this complex suggests new cellular trafficking events that may be important for the generation of dense-core vesicles.

scholarly journals Quantitative analysis of dense-core vesicle fusion in rodent CNS neurons

2021 ◽  
Vol 2 (1) ◽  
pp. 100325
Author(s):  
Alessandro Moro ◽  
Rein I. Hoogstraaten ◽  
Claudia M. Persoon ◽  
Matthijs Verhage ◽  
Ruud F. Toonen
Keyword(s):  
Quantitative Analysis ◽  
Vesicle Fusion ◽  
Dense Core ◽  
Dense Core Vesicle ◽  
Cns Neurons

scholarly journals Regulation of KIF1A-Driven Dense Core Vesicle Transport: Ca2+/CaM Controls DCV Binding and Liprin-α/TANC2 Recruits DCVs to Postsynaptic Sites

Cell Reports ◽  
2018 ◽  
Vol 24 (3) ◽  
pp. 685-700 ◽  
Author(s):  
Riccardo Stucchi ◽  
Gabriela Plucińska ◽  
Jessica J.A. Hummel ◽  
Eitan E. Zahavi ◽  
Irune Guerra San Juan ◽  
...  
Keyword(s):  
Vesicle Transport ◽  
Dense Core ◽  
Dense Core Vesicle

scholarly journals The Conserved VPS-50 Protein Functions in Dense-Core Vesicle Maturation and Acidification and Controls Animal Behavior

2016 ◽  
Vol 26 (7) ◽  
pp. 862-871 ◽  
Author(s):  
Nicolas Paquin ◽  
Yasunobu Murata ◽  
Allan Froehlich ◽  
Daniel T. Omura ◽  
Michael Ailion ◽  
...  
Keyword(s):  
Animal Behavior ◽  
Dense Core ◽  
Dense Core Vesicle ◽  
Protein Functions
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