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Peptide neuromodulators are released from a unique organelle: the dense-core vesicle. Dense-core vesicles are generated at the trans-Golgi and then sort cargo during maturation before being secreted. To identify proteins that act in this pathway, we performed a genetic screen in Caenorhabditis elegans for mutants defective in dense-core vesicle function. We identified two conserved Rab2-binding proteins: RUND-1, a RUN domain protein, and CCCP-1, a coiled-coil protein. RUND-1 and CCCP-1 colocalize with RAB-2 at the Golgi, and rab-2, rund-1, and cccp-1 mutants have similar defects in sorting soluble and transmembrane dense-core vesicle cargos. RUND-1 also interacts with the Rab2 GAP protein TBC-8 and the BAR domain protein RIC-19, a RAB-2 effector. In summary, a pathway of conserved proteins controls the maturation of dense-core vesicles at the trans-Golgi network.
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http://dx.doi.org/10.1016/j.neuron.2014.02.017 | DOI Listing |
Cell Tissue Res
September 2025
Institute for Anatomy and Cell Biology, German Center for Lung Research, Excellence Cluster Cardio-Pulmonary Institute (CPI), Justus Liebig University Giessen, 35392, Giessen, Germany.
Previous studies identified a rare cell type in the mouse tracheal epithelium with immunoreactivity to the microvillus protein villin (Vil1), which persisted in mice lacking tuft cells due to deletion of the transcription factor Pou2f3. This study aimed to clarify the identity of this ill-defined cell type. Ultrastructurally, all cells with tightly packed microvilli observed in the tracheal epithelium of Pou2f3-mice contained basally located dense core vesicles, a characteristic feature of neuroendocrine cells (NEC).
View Article and Find Full Text PDFExp Neurol
August 2025
Departamento de Anatomía, Histología y Neurociencia, Facultad de Medicina, Universidad Autónoma de Madrid, Arzobispo Morcillo 4, Madrid 28029, Spain. Electronic address:
The hypothalamic hypocretinergic/orexinergic (Hcrt/Ox) system comprises two neuropeptides -Hcrt1/OxA and Hcrt2/OxB- and two receptors -Hcrt/OxR1 and Hcrt/OxR2- which perform multiple modulatory actions. Its neurotransmission mechanism remains poorly understood despite its malfunction entails narcolepsy and low cerebrospinal fluid (CSF)-Hcrt1/OxA levels is the most specific biomarker of the disease. This work examines: (1) synaptic and volume Hcrt/Ox transmission types; (2) Hcrt/Ox receptors involvement in Hcrt/Ox-peptide release/synthesis; and (3) Hcrt/Ox system sexual dimorphism.
View Article and Find Full Text PDFPLoS Genet
July 2025
Department of Developmental, Molecular and Chemical Biology, Tufts University School of Medicine, Boston, Massachusetts, United States of America.
Regulation of AMPA Receptor (AMPAR) levels at synapses controls synaptic strength and is a major mechanism underlying learning and memory. Growing evidence indicates that AMPAR trafficking can be regulated by extracellular factors. Here, we show that the insulin-like peptide INS-27 mediates a muscle-to-neuron signal that promotes surface levels of the C.
View Article and Find Full Text PDFEMBO J
August 2025
Department of Physiology Anatomy and Genetics, University of Oxford, Oxford, UK.
Secretory proteins aggregate into non-soluble dense-core granules in recycling endosome-like compartments prior to regulated release. By contrast, aberrantly processed, secreted amyloid-β (Aβ) peptides derived from amyloid precursor protein (APP) form pathological extracellular amyloidogenic aggregations in late-stage Alzheimer's disease (AD). By examining living Drosophila prostate-like secondary cells, we show that both APP and Aβ peptides affect normal biogenesis of dense-core granules.
View Article and Find Full Text PDFTrafficking of intracellular cargoes along the neuronal axon microtubule tracks is a motor-protein-dependent process. It is well-established that the motor protein kinesin is responsible for anterograde trafficking of axonal cargo, while the dynein/dynactin complex regulates retrograde trafficking. However, there is still much to uncover regarding the various isoforms of these motor proteins as well as the adapter and cargo-associated proteins involved in the precise trafficking dynamics.
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