scholarly journals Ex Vivo Recording of Axonal Transport Dynamics on Postnatal Organotypic Cortical Slices

2020 ◽  
Vol 1 (3) ◽  
pp. 100131
Author(s):  
Silvia Turchetto ◽  
Loic Broix ◽  
Laurent Nguyen
Keyword(s):  
Axonal Transport ◽  
Ex Vivo ◽  
Transport Dynamics ◽  
Cortical Slices

scholarly journals KIF13A mediates the activity-dependent transport of ESCRT-0 proteins in axons

2020 ◽  
Author(s):  
Veronica Birdsall ◽  
Yuuta Imoto ◽  
Shigeki Watanabe ◽  
Clarissa L. Waites
Keyword(s):  
Axonal Transport ◽  
Neuronal Firing ◽  
Dependent Manner ◽  
Endosomal Sorting ◽  
Transport Dynamics ◽  
Transport Vesicles ◽  
Early Endosomes ◽  
Dependent Transport ◽  
Activity Dependent ◽  
Dependent Mechanism

AbstractTurnover of synaptic vesicle (SV) proteins is vital for the maintenance of healthy, functional synapses in neurons. Our previous work showed that the degradation of SV proteins is mediated by the endosomal sorting complex required for transport (ESCRT) pathway in an activity-dependent manner. Here, we characterize the axonal transport dynamics of ESCRT-0 proteins Hrs and STAM1, the first components of the ESCRT pathway critical for initiating SV protein degradation. Hrs- and STAM1-positive transport vesicles exhibit increased anterograde and bidirectional motility in response to neuronal firing, and frequent colocalization with SV pools. These ESCRT-0 vesicles are a subset of Rab5-positive structures in axons, likely representing pro-degradative early endosomes. Further, we identify kinesin motor protein KIF13A as essential for the activity-dependent transport of ESCRT-0 vesicles as well as the degradation of SV membrane proteins. Together, these data demonstrate a novel KIF13A-dependent mechanism for mobilizing axonal transport of ESCRT machinery to facilitate the degradation of SV proteins.

scholarly journals DYRK1A role in microtubule-based axonal transport regulates the retrograde dynamics of APP vesicles in human neurons

2021 ◽  
Author(s):  
Iván Fernandez Bessone ◽  
Karina Karmirian ◽  
Livia Goto-Silva ◽  
Mariana Holubiec ◽  
Jordi L. Navarro ◽  
...  
Keyword(s):  
Axonal Transport ◽  
Single Particle ◽  
Particle Dynamics ◽  
Transport Dynamics ◽  
Transport Regulation ◽  
Human Neurons ◽  
Custom Made ◽  
Relevant Role ◽  
Associated Proteins ◽  
Neuronal Distribution

AbstractIn Alzheimer’s Disease (AD) the abnormal intracellular distribution of the amyloid precursor protein (APP) affects its processing and, consequently, the generation of Aβ. Axonal transport plays key roles in the neuronal distribution of APP. The dual-specificity-tyrosine phosphorylation-regulated-kinase-1A (DYRK1A) has been associated with AD onset since its overexpression was found in Down syndrome and sporadic AD patients. Experimental evidence confirmed that APP and tau phosphorylations are mediated by DYRK1A. Moreover, DYRK1A can regulate the cytoskeletal architecture by phosphorylation of both tubulin subunits and microtubule-associated proteins. Therefore, we tested whether DYRK1A has a role in APP axonal transport regulation.We developed highly-polarized human-derived neurons in 2D cultures. At day 14 after terminal plating we inhibited DYRK1A for 48hs with harmine (7.5 μM). DYRK1A overexpression was induced to perform live-cell imaging of APP-loaded vesicles in axons and analyzed transport dynamics. A custom-made MATLAB routine was developed to track and analyze single particle dynamics.Short-term harmine treatment reduced axonal APP vesicles density, due to a reduction in retrograde particles. Contrarily, DYRK1A overexpression enhanced axonal APP density, due to an increase in the retrograde and stationary component. Moreover, both harmine-mediated DYRK1A inhibition and DYRK1A overexpression revealed opposite phenotypes on single particle dynamics, affecting primarily dynein processivity. These results revealed an increased retrieval of distal APP vesicles in axons when DYRK1A is overexpressed and reinforce the suggestion that DYRK1A enhance APP endocytosis‥Taken together our results suggest that DYRK1A has a relevant role in the regulation of axonal transport and sub-cellular positioning of APP vesicles. Therefore, our work shed light on the role of DYRK1A in axonal transport regulation, and the putative use of harmine to restore axonal transport impairments.

scholarly journals Microtubule Organization Determines Axonal Transport Dynamics

Neuron ◽  
2016 ◽  
Vol 92 (2) ◽  
pp. 449-460 ◽  
Author(s):  
Shaul Yogev ◽  
Roshni Cooper ◽  
Richard Fetter ◽  
Mark Horowitz ◽  
Kang Shen
Keyword(s):  
Axonal Transport ◽  
Microtubule Organization ◽  
Transport Dynamics

scholarly journals Emergence of directional bias in tau deposition from axonal transport dynamics

2021 ◽  
Vol 17 (7) ◽  
pp. e1009258
Author(s):  
Justin Torok ◽  
Pedro D. Maia ◽  
Parul Verma ◽  
Christopher Mezias ◽  
Ashish Raj
Keyword(s):  
Computational Model ◽  
Axonal Transport ◽  
Molecular Processes ◽  
Tau Pathology ◽  
Complex Interplay ◽  
Directional Bias ◽  
Neuron System ◽  
Transport Dynamics ◽  
Clinical Presentations ◽  
Disease Specific

Defects in axonal transport may partly underpin the differences between the observed pathophysiology of Alzheimer’s disease (AD) and that of other non-amyloidogenic tauopathies. Particularly, pathological tau variants may have molecular properties that dysregulate motor proteins responsible for the anterograde-directed transport of tau in a disease-specific fashion. Here we develop the first computational model of tau-modified axonal transport that produces directional biases in the spread of tau pathology. We simulated the spatiotemporal profiles of soluble and insoluble tau species in a multicompartment, two-neuron system using biologically plausible parameters and time scales. Changes in the balance of tau transport feedback parameters can elicit anterograde and retrograde biases in the distributions of soluble and insoluble tau between compartments in the system. Aggregation and fragmentation parameters can also perturb this balance, suggesting a complex interplay between these distinct molecular processes. Critically, we show that the model faithfully recreates the characteristic network spread biases in both AD-like and non-AD-like mouse tauopathy models. Tau transport feedback may therefore help link microscopic differences in tau conformational states and the resulting variety in clinical presentations.

scholarly journals Decoupling the Effects of the Amyloid Precursor Protein from Amyloid-β Plaques on Axonal Transport Dynamics in the Living Brain

2020 ◽  
Author(s):  
Christopher S Medina ◽  
Taylor W Uselman ◽  
Daniel R Barto ◽  
Frances Cháves ◽  
Russell E Jacobs ◽  
...  
Keyword(s):  
Amyloid Precursor Protein ◽  
Axonal Transport ◽  
Amyloid Β ◽  
Precursor Protein ◽  
Transport Dynamics

scholarly journals Emergence of directional bias in tau deposition from axonal transport dynamics

2021 ◽  
Author(s):  
Justin Torok ◽  
Pedro D Maia ◽  
Parul Verma ◽  
Christopher Mezias ◽  
Ashish Raj
Keyword(s):  
Computational Model ◽  
Axonal Transport ◽  
Molecular Processes ◽  
Tau Pathology ◽  
Complex Interplay ◽  
Directional Bias ◽  
Neuron System ◽  
Transport Dynamics ◽  
Clinical Presentations ◽  
Disease Specific

Defects in axonal transport may partly underpin the differences between the observed pathophysiology of Alzheimer's disease (AD) and that of other non-amyloidogenic tauopathies. Particularly, pathological tau variants may have molecular properties that dysregulate motor proteins responsible for the anterograde-directed transport of tau in a disease-specific fashion. Here we develop the first computational model of tau-modified axonal transport that produces directional biases in the spread of tau pathology. We simulated the spatiotemporal profiles of soluble and insoluble tau species in a multicompartment, two-neuron system using biologically plausible parameters and time scales. Changes in the balance of tau transport feedback parameters can elicit anterograde and retrograde biases in the distributions of soluble and insoluble tau between compartments in the system. Aggregation and fragmentation parameters can also perturb this balance, suggesting a complex interplay between these distinct molecular processes. Critically, we show that the model faithfully recreates the characteristic network spread biases in both AD-like and non-AD-like mouse tauopathy models. Tau transport feedback may therefore help link microscopic differences in tau conformational states and the resulting variety in clinical presentations.

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