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.

Single particle dynamics of supercooled water and the kinetic glass transition

1998 ◽  
Vol 08 (PR6) ◽  
pp. Pr6-109-Pr6-113
Author(s):  
P. Gallo ◽  
F. Sciortino ◽  
P. Tartaglia ◽  
S.-H. Chen
Keyword(s):  
Glass Transition ◽  
Single Particle ◽  
Supercooled Water ◽  
Particle Dynamics

Model for single-particle dynamics in supercooled water

1999 ◽  
Vol 59 (6) ◽  
pp. 6708-6714 ◽  
Author(s):  
S. H. Chen ◽  
C. Liao ◽  
F. Sciortino ◽  
P. Gallo ◽  
P. Tartaglia
Keyword(s):  
Single Particle ◽  
Supercooled Water ◽  
Particle Dynamics

scholarly journals Oligomeric amyloid-β induces early and widespread changes to the proteome in human iPSC-derived neurons

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Christopher Sackmann ◽  
Martin Hallbeck
Keyword(s):  
Amyloid Β ◽  
Brain Regions ◽  
Tau Proteins ◽  
Label Free ◽  
Human Neurons ◽  
Associated Proteins ◽  
Proteasome Subunits ◽  
Heterogeneous Nuclear Ribonucleoproteins ◽  
Human Ipsc ◽  
Differential Phosphorylation

AbstractAlzheimer’s disease (AD) is the most common form of dementia globally and is characterized by aberrant accumulations of amyloid-beta (Aβ) and tau proteins. Oligomeric forms of these proteins are believed to be most relevant to disease progression, with oligomeric amyloid-β (oAβ) particularly implicated in AD. oAβ pathology spreads among interconnected brain regions, but how oAβ induces pathology in these previously unaffected neurons requires further study. Here, we use well characterized iPSC-derived human neurons to study the early changes to the proteome and phosphoproteome after 24 h exposure to oAβ 1-42. Using nLC-MS/MS and label-free quantification, we identified several proteins that are differentially regulated in response to acute oAβ challenge. At this early timepoint, oAβ induced the decrease of TDP-43, heterogeneous nuclear ribonucleoproteins (hnRNPs), and coatomer complex I (COPI) proteins. Conversely, increases were observed in 20 S proteasome subunits and vesicle associated proteins VAMP1/2, as well as the differential phosphorylation of tau at serine 208. These changes show that there are widespread alterations to the neuronal proteome within 24 h of oAβ uptake, including proteins previously not shown to be related to neurodegeneration. This study provides new targets for the further study of early mediators of AD pathogenesis.

scholarly journals The cell wall regulates dynamics and size of plasma-membrane nanodomains inArabidopsis

2019 ◽  
Vol 116 (26) ◽  
pp. 12857-12862 ◽  
Author(s):  
J. F. McKenna ◽  
D. J. Rolfe ◽  
S. E. D. Webb ◽  
A. F. Tolmie ◽  
S. W. Botchway ◽  
...  
Keyword(s):  
Cell Wall ◽  
Plasma Membrane ◽  
Confocal Microscopy ◽  
Particle Tracking ◽  
Single Particle ◽  
Cluster Size ◽  
Particle Dynamics ◽  
Single Particle Tracking ◽  
Signaling Cascade ◽  
Plant Plasma Membrane

Plant plasma-membrane (PM) proteins are involved in several vital processes, such as detection of pathogens, solute transport, and cellular signaling. For these proteins to function effectively there needs to be structure within the PM allowing, for example, proteins in the same signaling cascade to be spatially organized. Here we demonstrate that several proteins with divergent functions are located in clusters of differing size in the membrane using subdiffraction-limited Airyscan confocal microscopy. Single particle tracking reveals that these proteins move at different rates within the membrane. Actin and microtubule cytoskeletons appear to significantly regulate the mobility of one of these proteins (the pathogen receptor FLS2) and we further demonstrate that the cell wall is critical for the regulation of cluster size by quantifying single particle dynamics of proteins with key roles in morphogenesis (PIN3) and pathogen perception (FLS2). We propose a model in which the cell wall and cytoskeleton are pivotal for regulation of protein cluster size and dynamics, thereby contributing to the formation and functionality of membrane nanodomains.

scholarly journals Crossover from picosecond collective to single particle dynamics defines the mechanism of lateral lipid diffusion

2018 ◽  
Vol 1860 (11) ◽  
pp. 2446-2455 ◽  
Author(s):  
Dima Bolmatov ◽  
Yong Q. Cai ◽  
Dmitry Zav’yalov ◽  
Mikhail Zhernenkov
Keyword(s):  
Single Particle ◽  
Particle Dynamics ◽  
Lipid Diffusion

Experience with online modeling tools during the CBETA fractional arc test and single pass commissioning

2019 ◽  
Vol 34 (36) ◽  
pp. 1942039
Author(s):  
C. Gulliford ◽  
D. Sagan ◽  
A. Bartnik ◽  
J. Dobbins ◽  
J. S. Berg ◽  
...  
Keyword(s):  
Control System ◽  
Single Particle ◽  
Energy Recovery ◽  
Particle Dynamics ◽  
Initial Experience ◽  
Online Program ◽  
Modeling Tools ◽  
Online Modeling ◽  
Energy Recovery Linac ◽  
Pass Energy

The Cornell-Brookhaven CBETA machine is a four-pass Energy Recovery Linac (ERL) with a Non-scaling Fixed-Field Alternating gradient (NS-FFA) arc. For online modeling of single particle dynamics in CBETA, a customized version of the Tao program, which is based upon the Bmad toolkit, has been developed. This online program, called CBETA-V, is interfaced to CBETA’s EPICS control system. This work describes the online modeling system and initial experience during machine running, as well as subsequent developments since its first implementation.

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