Keeping Neuronal Cargoes on the Right Track: New Insights into Regulators of Axonal Transport

2016 ◽  
Vol 23 (3) ◽  
pp. 232-250 ◽  
Author(s):  
Kenneth G. Miller
Keyword(s):  
Retrograde Transport ◽  
Dense Core ◽  
System Model ◽  
Dense Core Vesicles ◽  
C Elegans ◽  
Early Endosomes ◽  
New Findings ◽  
Active Zones ◽  
The Right ◽  
Suppressor Screen

In neurons, a single motor (dynein) transports large organelles as well as synaptic and dense core vesicles toward microtubule minus ends; however, it is unclear why dynein appears more active on organelles, which are generally excluded from mature axons, than on synaptic and dense core vesicles, which are maintained at high levels. Recent studies in Zebrafish and Caenorhabditis elegans have shown that JIP3 promotes dynein-mediated retrograde transport to clear some organelles (lysosomes, early endosomes, and Golgi) from axons and prevent their potentially harmful accumulation in presynaptic regions. A JIP3 mutant suppressor screen in C. elegans revealed that JIP3 promotes the clearance of organelles from axons by blocking the action of the CSS system (Cdk5, SAD Kinase, SYD-2/Liprin). A synthesis of results in vertebrates with the new findings suggests that JIP3 blocks the CSS system from disrupting the connection between dynein and organelles. Most components of the CSS system are enriched at presynaptic active zones where they normally contribute to maintaining optimal levels of captured synaptic and dense core vesicles, in part by inhibiting dynein transport. The JIP3-CSS system model explains how neurons selectively regulate a single minus-end motor to exclude specific classes of organelles from axons, while at the same time ensuring optimal levels of synaptic and dense core vesicles.

scholarly journals Automated classification of synaptic vesicles in electron tomograms of C. elegans using machine learning

2018 ◽  
Author(s):  
Kristin Verena Kaltdorf ◽  
Maria Theiss ◽  
Sebastian Matthias Markert ◽  
Mei Zhen ◽  
Thomas Dandekar ◽  
...  
Keyword(s):  
Machine Learning ◽  
Synaptic Vesicles ◽  
Egg Laying ◽  
Dense Core ◽  
Dense Core Vesicles ◽  
Ground Truth Data ◽  
Neuronal Signaling ◽  
C Elegans ◽  
Morphological Criteria ◽  
Combine Machine

1.AbstractSynaptic vesicles (SVs) are a key component of neuronal signaling and fulfil different roles depending on their composition. In electron micrograms of neurites, two types of vesicles can be distinguished by morphological criteria, the classical “clear core” vesicles (CCV) and the typically larger “dense core” vesicles (DCV), with differences in electron density due to their diverse cargos. Compared to CCVs, the precise function of DCVs is less defined. DCVs are known to store neuropeptides, which function as neuronal messengers and modulators [1]. In C. elegans, they play a role in locomotion, dauer formation, egg-laying, and mechano- and chemosensation [2]. Another type of DCVs, also referred to as granulated vesicles, are known to transport Bassoon, Piccolo and further constituents of the presynaptic density in the center of the active zone (AZ), and therefore are important for synaptogenesis [3].To better understand the role of different types of SVs, we present here a new automated approach to classify vesicles. We combine machine learning with an extension of our previously developed vesicle segmentation workflow, the ImageJ macro 3D ART VeSElecT. With that we reliably distinguish CCVs and DCVs in electron tomograms of C. elegans NMJs using image-based features. Analysis of the underlying ground truth data shows an increased fraction of DCVs as well as a higher mean distance between DCVs and AZs in dauer larvae compared to young adult hermaphrodites. Our machine learning based tools are adaptable and can be applied to study properties of different synaptic vesicle pools in electron tomograms of diverse model organisms.2.Author summaryVesicles are important components of the cell, and synaptic vesicles are central for neuronal signaling. Two types of synaptic vesicles can be distinguished by electron microscopy: the classical “clear core” vesicles (CCVs) and the typically larger “dense core” vesicles (DCVs). The distinct appearance of vesicles is caused by their different cargos. To rapidly distinguish between both vesicle types, we present here a new automated approach to classify vesicles in electron tomograms. We combine machine learning with an extension of our previously developed vesicle segmentation workflow, an ImageJ macro, to reliably distinguish CCVs and DCVs using specific image-based features. The approach was trained and validated using data-sets that were hand curated by microscopy experts. Our technique can be transferred to more extensive comparisons in both stages as well as to other neurobiology questions regarding synaptic vesicles.

UNC-31/CAPS docks and primes dense core vesicles in C. elegans neurons

2010 ◽  
Vol 397 (3) ◽  
pp. 526-531 ◽  
Author(s):  
Xian-Guang Lin ◽  
Min Ming ◽  
Mao-Rong Chen ◽  
Wei-Pin Niu ◽  
Yong-Deng Zhang ◽  
...  
Keyword(s):  
Dense Core ◽  
Dense Core Vesicles ◽  
C Elegans

A Model of Neuropeptide Transport in Various Types of Nerve Terminals Containing En Passant Boutons: The Effect of the Rate of Neuropeptide Production in the Neuron Soma

2015 ◽  
Author(s):  
I. A. Kuznetsov ◽  
A. V. Kuznetsov
Keyword(s):  
Mathematical Model ◽  
Production Rate ◽  
Retrograde Transport ◽  
Dense Core ◽  
Experimental Results ◽  
Nerve Terminals ◽  
Dense Core Vesicles ◽  
Type Iii ◽  
Neuropeptide Release ◽  
Neuron Soma

After being synthesized in the soma, neuropeptides are packaged in dense core vesicles (DCVs) and transported toward nerve terminals. It is known, from published experimental results, that in terminals with type Ib boutons DCVs circulate in the terminal, undergoing repeated anterograde and retrograde transport, while in type III terminals DCVs do not circulate in the terminal. Our goal here is to investigate whether the increased DCV production in the soma can lead to the appearance of DCV circulation in type III boutons. For this purpose we developed a mathematical model that simulates DCV transport in various terminals. Our model reproduces some important experimental results, such as those concerning DCV circulation in type Ib and type III terminals. We used the developed model to make testable predictions. The model predicts that an increased DCV production rate in the soma leads to increased DCV circulation in type Ib boutons and to the appearance of DCV circulation in type III boutons. The model also predicts that there are different stages in the development of DCV circulation in the terminals after they were depleted of DCVs due to neuropeptide release.

scholarly journals Vacuolar H+-ATPase subunits Voa1 and Voa2 cooperatively regulate secretory vesicle acidification, transmitter uptake, and storage

2011 ◽  
Vol 22 (18) ◽  
pp. 3394-3409 ◽  
Author(s):  
Ner Mu Nar Saw ◽  
Soo-Young Ann Kang ◽  
Leon Parsaud ◽  
Gayoung Anna Han ◽  
Tiandan Jiang ◽  
...  
Keyword(s):  
Pc12 Cells ◽  
Secretory Vesicle ◽  
Dense Core ◽  
Dense Core Vesicles ◽  
Functional Roles ◽  
Early Endosomes ◽  
Atpase Subunits ◽  
Peptide Secretion ◽  
Transmitter Uptake ◽  
And Storage

The Vo sector of the vacuolar H+-ATPase is a multisubunit complex that forms a proteolipid pore. Among the four isoforms (a1–a4) of subunit Voa, the isoform(s) critical for secretory vesicle acidification have yet to be identified. An independent function of Voa1 in exocytosis has been suggested. Here we investigate the function of Voa isoforms in secretory vesicle acidification and exocytosis by using neurosecretory PC12 cells. Fluorescence-tagged and endogenous Voa1 are primarily localized on secretory vesicles, whereas fluorescence-tagged Voa2 and Voa3 are enriched on the Golgi and early endosomes, respectively. To elucidate the functional roles of Voa1 and Voa2, we engineered PC12 cells in which Voa1, Voa2, or both are stably down-regulated. Our results reveal significant reductions in the acidification and transmitter uptake/storage of dense-core vesicles by knockdown of Voa1 and more dramatically of Voa1/Voa2 but not of Voa2. Overexpressing knockdown-resistant Voa1 suppresses the acidification defect caused by the Voa1/Voa2 knockdown. Unexpectedly, Ca2+-dependent peptide secretion is largely unaffected in Voa1 or Voa1/Voa2 knockdown cells. Our data demonstrate that Voa1 and Voa2 cooperatively regulate the acidification and transmitter uptake/storage of dense-core vesicles, whereas they might not be as critical for exocytosis as recently proposed.

scholarly journals PKA Activation Bypasses the Requirement for UNC-31 in the Docking of Dense Core Vesicles from C. elegans Neurons

Neuron ◽  
2007 ◽  
Vol 56 (4) ◽  
pp. 657-669 ◽  
Author(s):  
Ke-Ming Zhou ◽  
Yong-Ming Dong ◽  
Qian Ge ◽  
Dan Zhu ◽  
Wei Zhou ◽  
...  
Keyword(s):  
Dense Core ◽  
Dense Core Vesicles ◽  
C Elegans

scholarly journals Mechanism of uptake and retrograde axonal transport of noradrenaline in sympathetic neurons in culture: reserpine-resistant large dense-core vesicles as transport vehicles.

1983 ◽  
Vol 96 (6) ◽  
pp. 1538-1547 ◽  
Author(s):  
M E Schwab ◽  
H Thoenen
Keyword(s):  
Axonal Transport ◽  
Sympathetic Neurons ◽  
Retrograde Transport ◽  
Retrograde Axonal Transport ◽  
Dense Core ◽  
Substantial Part ◽  
Culture Dish ◽  
Dense Core Vesicles ◽  
Large Dense Core Vesicles ◽  
Amine Uptake

The uptake and retrograde transport of noradrenaline (NA) within the axons of sympathetic neurons was investigated in an in vitro system. Dissociated neurons from the sympathetic ganglia of newborn rats were cultured for 3-6 wk in the absence of non-neuronal cells in a culture dish divided into three chambers. These allowed separate access to the axonal networks and to their cell bodies of origin. [3H]NA (0.5 X 10(-6) M), added to the axon chambers, was taken up by the desmethylimipramine- and cocaine-sensitive neuronal amine uptake mechanisms, and a substantial part was rapidly transported retrogradely along the axons to the nerve cell bodies. This transport was blocked by vinblastine or colchicine. In contrast with the storage of [3H]NA in the axonal varicosities, which was totally prevented by reserpine (a drug that selectively inactivates the uptake of NA into adrenergic storage vesicles), the retrograde transport of [3H]NA was only slightly diminished by reserpine pretreatment. Electron microscopic localization of the NA analogue 5-hydroxydopamine (5-OHDA) indicated that mainly large dense-core vesicles (700-1,200-A diam) are the transport compartment involved. Whereas the majority of small and large vesicles lost their amine dense-core and were resistant to this drug. It, therefore, seems that these vesicles maintained the amine uptake and storage mechanisms characteristic for adrenergic vesicles, but have lost the sensitivity of their amine carrier for reserpine. The retrograde transport of NA and 5-OHDA probably reflects the return of used synaptic vesicle membrane to the cell body in a form that is distinct from the membranous cisternae and prelysosomal structures involved in the retrograde axonal transport of extracellular tracers.

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