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Stress Conditions Increase Vimentin Cleavage by Omi/HtrA2 Protease in Human Primary Neurons and Differentiated Neuroblastoma Cells

Overview of attention for article published in Molecular Neurobiology, October 2014
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Title
Stress Conditions Increase Vimentin Cleavage by Omi/HtrA2 Protease in Human Primary Neurons and Differentiated Neuroblastoma Cells
Published in
Molecular Neurobiology, October 2014
DOI 10.1007/s12035-014-8906-3
Pubmed ID
Authors

Bérangère Lucotte, Mehdi Tajhizi, Dareen Alkhatib, Eva-Britt Samuelsson, Birgitta Wiehager, Sophia Schedin-Weiss, Erik Sundström, Bengt Winblad, Lars.O Tjernberg, Homira Behbahani

Abstract

Dysfunctional Omi/HtrA2, a mitochondrial serine protease, has been implicated in various neurodegenerative disorders. Despite the wealth of evidence on the roles of Omi/HtrA2 in apoptosis, little is known about its cytosolic targets, the cleavage of which could account for the observed morphological changes such as cytoskeletal reorganizations in axons. By proteomic analysis, vimentin was identified as a substrate for Omi/HtrA2 and we have reported increased Omi/HtrA2 protease activity in Alzheimer disease (AD) brain. Here, we investigated a possible link between Omi/HtrA2 and vimentin cleavage, and consequence of this cleavage on mitochondrial distribution in neurons. In vitro protease assays showed vimentin to be cleaved by Omi/HtrA2 protease, and proximity ligation assay demonstrated an increased interaction between Omi/HtrA2 and vimentin in human primary neurons upon stress stimuli. Using differentiated neuroblastoma SH-SY5Y cells, we showed that Omi/HtrA2 under several different stress conditions induces cleavage of vimentin in wild-type as well as SH-SY5Y cells transfected with amyloid precursor protein with the Alzheimer disease-associated Swedish mutation. After stress treatment, inhibition of Omi/HtrA2 protease activity by the Omi/HtrA2 specific inhibitor, Ucf-101, reduced the cleavage of vimentin in wild-type cells. Following altered vimentin filaments integrity by stress stimuli, mitochondria was redistributed in differentiated SH-SY5Y cells and human primary neurons. In summary, the findings outlined in this paper suggest a role of Omi/HtrA2 in modulation of vimentin filamentous structure in neurons. Our results provide important findings for understanding the biological role of Omi/HtrA2 activity during stress conditions, and give knowledge of interplay between Omi/HtrA2 and vimentin which might affect mitochondrial distribution in neurons.

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Mendeley readers

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The data shown below were compiled from readership statistics for 48 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 48 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 11 23%
Student > Bachelor 8 17%
Researcher 7 15%
Student > Master 6 13%
Other 2 4%
Other 6 13%
Unknown 8 17%
Readers by discipline Count As %
Agricultural and Biological Sciences 10 21%
Biochemistry, Genetics and Molecular Biology 9 19%
Medicine and Dentistry 5 10%
Neuroscience 5 10%
Environmental Science 2 4%
Other 8 17%
Unknown 9 19%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 09 October 2014.
All research outputs
#20,238,443
of 22,765,347 outputs
Outputs from Molecular Neurobiology
#2,778
of 3,440 outputs
Outputs of similar age
#213,119
of 255,128 outputs
Outputs of similar age from Molecular Neurobiology
#45
of 72 outputs
Altmetric has tracked 22,765,347 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 3,440 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.2. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
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