scholarly journals Rab2 drives axonal transport of dense core vesicles and lysosomal organelles

Cell Reports ◽  
2021 ◽  
Vol 35 (2) ◽  
pp. 108973
Author(s):  
Viktor Karlovich Lund ◽  
Matthew Domenic Lycas ◽  
Anders Schack ◽  
Rita Chan Andersen ◽  
Ulrik Gether ◽  
...  
Keyword(s):  
Axonal Transport ◽  
Dense Core ◽  
Dense Core Vesicles

scholarly journals Rab2 drives axonal transport of dense core vesicles and lysosomal organelles

2020 ◽  
Author(s):  
Viktor K. Lund ◽  
Matthew D. Lycas ◽  
Anders Schack ◽  
Rita C. Andersen ◽  
Ulrik Gether ◽  
...  
Keyword(s):  
Axonal Transport ◽  
Long Range ◽  
Molecular Motors ◽  
Critical Role ◽  
Model System ◽  
Small Gtpase ◽  
Dense Core ◽  
Fast Axonal Transport ◽  
Dense Core Vesicles ◽  
Motility Factor

SUMMARYLong range fast axonal transport of neuropeptide-containing dense core vesicles (DCVs), endolysosomal organelles and presynaptic components is critical for maintaining the functionality of neurons. How the transport of DCVs is orchestrated remains an important unresolved question. The small GTPase Rab2 has previously been shown to mediate DCV biogenesis and endosome-lysosome fusion. Here we use the Drosophila model system to demonstrate that Rab2 also plays a critical role in bidirectional axonal transport of DCVs, endosomes and lysosomal organelles, most likely by controlling molecular motors. We further show that the lysosomal motility factor Arl8 is required as well for axonal transport of DCVs, but unlike Rab2 is also critical for DCV exit from cell bodies into axons. Our results uncover the mechanisms responsible for axonal transport of DCVs and reveal surprising parallels between the regulation of DCVs and lysosomal motility.

scholarly journals Rab2 Drives Axonal Transport of Dense Core Vesicles and Lysosomal Organelles

2020 ◽  
Author(s):  
Viktor K. Lund ◽  
Matthew D. Lycas ◽  
Anders Schack ◽  
Rita C. Andersen ◽  
Ulrik Gether ◽  
...  
Keyword(s):  
Axonal Transport ◽  
Dense Core ◽  
Dense Core Vesicles

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.

scholarly journals A STRIPAK complex mediates axonal transport of autophagosomes and dense core vesicles through PP2A regulation

2017 ◽  
Vol 216 (2) ◽  
pp. 441-461 ◽  
Author(s):  
Amanda L. Neisch ◽  
Thomas P. Neufeld ◽  
Thomas S. Hays
Keyword(s):  
Axonal Transport ◽  
Essential Role ◽  
Motor Coordination ◽  
Dense Core ◽  
Regulatory Subunit ◽  
Dense Core Vesicles ◽  
Cellular Homeostasis ◽  
Cellular Debris ◽  
Core Components ◽  
Clearance Process

Autophagy plays an essential role in the cellular homeostasis of neurons, facilitating the clearance of cellular debris. This clearance process is orchestrated through the assembly, transport, and fusion of autophagosomes with lysosomes for degradation. The motor protein dynein drives autophagosome motility from distal sites of assembly to sites of lysosomal fusion. In this study, we identify the scaffold protein CKA (connector of kinase to AP-1) as essential for autophagosome transport in neurons. Together with other core components of the striatin-interacting phosphatase and kinase (STRIPAK) complex, we show that CKA associates with dynein and directly binds Atg8a, an autophagosomal protein. CKA is a regulatory subunit of PP2A, a component of the STRIPAK complex. We propose that the STRIPAK complex modulates dynein activity. Consistent with this hypothesis, we provide evidence that CKA facilitates axonal transport of dense core vesicles and autophagosomes in a PP2A-dependent fashion. In addition, CKA-deficient flies exhibit PP2A-dependent motor coordination defects. CKA function within the STRIPAK complex is crucial to prevent transport defects that may contribute to neurodegeneration.

scholarly journals Mycalolide B dissociates dynactin and abolishes retrograde axonal transport of dense-core vesicles

2015 ◽  
Vol 26 (14) ◽  
pp. 2664-2672 ◽  
Author(s):  
Samantha L. Cavolo ◽  
Chaoming Zhou ◽  
Stephanie A. Ketcham ◽  
Matthew M. Suzuki ◽  
Kresimir Ukalovic ◽  
...  
Keyword(s):  
Axonal Transport ◽  
Nerve Terminal ◽  
Retrograde Transport ◽  
Cell Extract ◽  
Retrograde Axonal Transport ◽  
Amino Acid Sequences ◽  
Dense Core ◽  
Dense Core Vesicles ◽  
Anterograde Transport ◽  
Transport Inhibition

Axonal transport is critical for maintaining synaptic transmission. Of interest, anterograde and retrograde axonal transport appear to be interdependent, as perturbing one directional motor often impairs movement in the opposite direction. Here live imaging of Drosophila and hippocampal neuron dense-core vesicles (DCVs) containing a neuropeptide or brain-derived neurotrophic factor shows that the F-actin depolymerizing macrolide toxin mycalolide B (MB) rapidly and selectively abolishes retrograde, but not anterograde, transport in the axon and the nerve terminal. Latrunculin A does not mimic MB, demonstrating that F-actin depolymerization is not responsible for unidirectional transport inhibition. Given that dynactin initiates retrograde transport and that amino acid sequences implicated in macrolide toxin binding are found in the dynactin component actin-related protein 1, we examined dynactin integrity. Remarkably, cell extract and purified protein experiments show that MB induces disassembly of the dynactin complex. Thus imaging selective retrograde transport inhibition led to the discovery of a small-molecule dynactin disruptor. The rapid unidirectional inhibition by MB suggests that dynactin is absolutely required for retrograde DCV transport but does not directly facilitate ongoing anterograde DCV transport in the axon or nerve terminal. More generally, MB's effects bolster the conclusion that anterograde and retrograde axonal transport are not necessarily interdependent.

Relationship between golgi apparatus and axonal reticulum in sympathetic ganglion cells

1978 ◽  
Vol 36 (2) ◽  
pp. 598-599
Author(s):  
J. Quatacker ◽  
W. De Potter
Keyword(s):  
Golgi Apparatus ◽  
Sympathetic Ganglion ◽  
Phosphotungstic Acid ◽  
Ganglion Cells ◽  
Low Ph ◽  
Dense Core ◽  
Dense Core Vesicles ◽  
Large Dense Core Vesicles ◽  
Cervical Ganglia ◽  
Axoplasmic Reticulum

Mucopolysaccharides have been demonstrated biochemically in catecholamine-containing subcellular particles in different rat, cat and ox tissues. As catecholamine-containing granules seem to arise from the Golgi apparatus and some also from the axoplasmic reticulum we examined wether carbohydrate macromolecules could be detected in the small and large dense core vesicles and in structures related to them. To this purpose superior cervical ganglia and irises from rabbit and cat and coeliac ganglia and their axons from dog were subjected to the chromaffin reaction to show the distribution of catecholamine-containing granules. Some material was also embedded in glycolmethacrylate (GMA) and stained with phosphotungstic acid (PTA) at low pH for the detection of carbohydrate macromolecules.The chromaffin reaction in the perikarya reveals mainly large dense core vesicles, but in the axon hillock, the axons and the terminals, the small dense core vesicles are more prominent. In the axons the small granules are sometimes seen inside a reticular network (fig. 1).

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