scholarly journals CAPS-1 promotes fusion competence of stationary dense-core vesicles in presynaptic terminals of mammalian neurons

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Margherita Farina ◽  
Rhea van de Bospoort ◽  
Enqi He ◽  
Claudia M Persoon ◽  
Jan RT van Weering ◽  
...  
Keyword(s):  
Dense Core ◽  
Null Mutant ◽  
Dense Core Vesicles ◽  
Presynaptic Terminals ◽  
Synaptic Localization ◽  
Calcium Dependent ◽  
Synaptic Markers ◽  
Fusion Probability ◽  
Single Vesicle

Neuropeptides released from dense-core vesicles (DCVs) modulate neuronal activity, but the molecules driving DCV secretion in mammalian neurons are largely unknown. We studied the role of calcium-activator protein for secretion (CAPS) proteins in neuronal DCV secretion at single vesicle resolution. Endogenous CAPS-1 co-localized with synaptic markers but was not enriched at every synapse. Deletion of CAPS-1 and CAPS-2 did not affect DCV biogenesis, loading, transport or docking, but DCV secretion was reduced by 70% in CAPS-1/CAPS-2 double null mutant (DKO) neurons and remaining fusion events required prolonged stimulation. CAPS deletion specifically reduced secretion of stationary DCVs. CAPS-1-EYFP expression in DKO neurons restored DCV secretion, but CAPS-1-EYFP and DCVs rarely traveled together. Synaptic localization of CAPS-1-EYFP in DKO neurons was calcium dependent and DCV fusion probability correlated with synaptic CAPS-1-EYFP expression. These data indicate that CAPS-1 promotes fusion competence of immobile (tethered) DCVs in presynaptic terminals and that CAPS-1 localization to DCVs is probably not essential for this role.

scholarly journals Correction: CAPS-1 promotes fusion competence of stationary dense-core vesicles in presynaptic terminals of mammalian neurons

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Margherita Farina ◽  
Rhea van de Bospoort ◽  
Enqi He ◽  
Claudia M Persoon ◽  
Jan RT van Weering ◽  
...  
Keyword(s):  
Dense Core ◽  
Dense Core Vesicles ◽  
Presynaptic Terminals

scholarly journals Synaptotagmin V Is Targeted to Dense-core Vesicles That Undergo Calcium-dependent Exocytosis in PC12 Cells

2002 ◽  
Vol 277 (27) ◽  
pp. 24499-24505 ◽  
Author(s):  
Chika Saegusa ◽  
Mitsunori Fukuda ◽  
Katsuhiko Mikoshiba
Keyword(s):  
Pc12 Cells ◽  
Dense Core ◽  
Dense Core Vesicles ◽  
Calcium Dependent

scholarly journals Resident CAPS on dense-core vesicles docks and primes vesicles for fusion

2016 ◽  
Vol 27 (4) ◽  
pp. 654-668 ◽  
Author(s):  
Greg Kabachinski ◽  
D. Michelle Kielar-Grevstad ◽  
Xingmin Zhang ◽  
Declan J. James ◽  
Thomas F. J. Martin
Keyword(s):  
Plasma Membrane ◽  
Pc12 Cells ◽  
Protein Complexes ◽  
Neuroendocrine Cells ◽  
Dense Core ◽  
Snare Complex ◽  
Snare Protein ◽  
Dense Core Vesicles ◽  
Vesicle Docking ◽  
Single Vesicle

The Ca2+-dependent exocytosis of dense-core vesicles in neuroendocrine cells requires a priming step during which SNARE protein complexes assemble. CAPS (aka CADPS) is one of several factors required for vesicle priming; however, the localization and dynamics of CAPS at sites of exocytosis in live neuroendocrine cells has not been determined. We imaged CAPS before, during, and after single-vesicle fusion events in PC12 cells by TIRF micro­scopy. In addition to being a resident on cytoplasmic dense-core vesicles, CAPS was present in clusters of approximately nine molecules near the plasma membrane that corresponded to docked/tethered vesicles. CAPS accompanied vesicles to the plasma membrane and was present at all vesicle exocytic events. The knockdown of CAPS by shRNA eliminated the VAMP-2–dependent docking and evoked exocytosis of fusion-competent vesicles. A CAPS(ΔC135) protein that does not localize to vesicles failed to rescue vesicle docking and evoked exocytosis in CAPS-depleted cells, showing that CAPS residence on vesicles is essential. Our results indicate that dense-core vesicles carry CAPS to sites of exocytosis, where CAPS promotes vesicle docking and fusion competence, probably by initiating SNARE complex assembly.

Specific KIF1A–adaptor interactions control selective cargo recognition

2021 ◽  
Vol 220 (10) ◽  
Author(s):  
Jessica J.A. Hummel ◽  
Casper C. Hoogenraad
Keyword(s):  
Motor Activity ◽  
Family Member ◽  
Posttranslational Modifications ◽  
Molecular Motors ◽  
Synaptic Vesicles ◽  
Intracellular Transport ◽  
Dense Core ◽  
Dense Core Vesicles ◽  
Transport Vesicles

Intracellular transport in neurons is driven by molecular motors that carry many different cargos along cytoskeletal tracks in axons and dendrites. Identifying how motors interact with specific types of transport vesicles has been challenging. Here, we use engineered motors and cargo adaptors to systematically investigate the selectivity and regulation of kinesin-3 family member KIF1A–driven transport of dense core vesicles (DCVs), lysosomes, and synaptic vesicles (SVs). We dissect the role of KIF1A domains in motor activity and show that CC1 regulates autoinhibition, CC2 regulates motor dimerization, and CC3 and PH mediate cargo binding. Furthermore, we identify that phosphorylation of KIF1A is critical for binding to vesicles. Cargo specificity is achieved by specific KIF1A adaptors; MADD/Rab3GEP links KIF1A to SVs, and Arf-like GTPase Arl8A mediates interactions with DCVs and lysosomes. We propose a model where motor dimerization, posttranslational modifications, and specific adaptors regulate selective KIF1A cargo trafficking.

scholarly journals Tomosyn inhibits priming of large dense-core vesicles in a calcium-dependent manner

2004 ◽  
Vol 101 (8) ◽  
pp. 2578-2583 ◽  
Author(s):  
O. Yizhar ◽  
U. Matti ◽  
R. Melamed ◽  
Y. Hagalili ◽  
D. Bruns ◽  
...  
Keyword(s):  
Dense Core ◽  
Dependent Manner ◽  
Dense Core Vesicles ◽  
Calcium Dependent ◽  
Large Dense Core Vesicles

scholarly journals APP accumulates around dense-core amyloid plaques with presynaptic proteins in Alzheimer’s disease brain

2020 ◽  
Author(s):  
Tomàs Jordà-Siquier ◽  
Melina Petrel ◽  
Vladimir Kouskoff ◽  
Fabrice Cordelières ◽  
Susanne Frykman ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Plaques ◽  
Dense Core ◽  
Subcellular Compartment ◽  
Aβ Peptides ◽  
Synaptic Markers ◽  
Analytical Tools ◽  
Presynaptic Proteins

SummaryIn Alzheimer’s disease (AD), a central role is given to the extracellular deposition of Aβ peptides, remotely produced by the proteolysis of the amyloid precursor protein (APP). This contrasts with other neurodegenerative diseases which are characterized by the intraneuronal aggregation of full-length proteins such as huntingtin, α-synuclein or TDP-43. Importantly, the distribution of APP around amyloid plaques is poorly characterized. Here, we combined an extensive set of methodological and analytical tools to investigate neuropathological features of APP in the human AD hippocampus and in two mouse models of AD. We report that APP remarkably accumulates in the surrounding of dense-core amyloid plaques together with the secretases necessary to produce Aβ peptides. In addition, the Nter domain, but not the Cter domain of APP is enriched in the core of amyloid plaques uncovering a potential pathological role of the secreted APP-Nter in dense-core plaques. To investigate the subcellular compartment in which APP accumulates, we labelled neuritic and synaptic markers and report an enrichment in presynaptic proteins (Syt1, VAMP2) and phosphorylated-Tau. Ultrastructural analysis of APP accumulations reveals abundant multivesicular bodies containing presynaptic vesicles proteins and autophagosomal built-up of APP. Altogether, our data supports a role of presynaptic APP in AD pathology and highlights APP accumulations as a potential source of Aβ and Nter peptides to fuel amyloid plaques.

Sign in / Sign up

Export Citation Format

Share Document