C9ORF72 interaction with cofilin modulates actin dynamics in motor neurons

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Standard

C9ORF72 interaction with cofilin modulates actin dynamics in motor neurons. / Sivadasan, Rajeeve; Hornburg, Daniel; Drepper, Carsten; Frank, Nicolas; Jablonka, Sibylle; Hansel, Anna; Lojewski, Xenia; Sterneckert, Jared; Hermann, Andreas; Shaw, Pamela J; Ince, Paul G; Mann, Matthias; Meissner, Felix; Sendtner, Michael.

I: Nature Neuroscience, Bind 19, Nr. 12, 12.2016, s. 1610-1618.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Sivadasan, R, Hornburg, D, Drepper, C, Frank, N, Jablonka, S, Hansel, A, Lojewski, X, Sterneckert, J, Hermann, A, Shaw, PJ, Ince, PG, Mann, M, Meissner, F & Sendtner, M 2016, 'C9ORF72 interaction with cofilin modulates actin dynamics in motor neurons', Nature Neuroscience, bind 19, nr. 12, s. 1610-1618. https://doi.org/10.1038/nn.4407

APA

Sivadasan, R., Hornburg, D., Drepper, C., Frank, N., Jablonka, S., Hansel, A., Lojewski, X., Sterneckert, J., Hermann, A., Shaw, P. J., Ince, P. G., Mann, M., Meissner, F., & Sendtner, M. (2016). C9ORF72 interaction with cofilin modulates actin dynamics in motor neurons. Nature Neuroscience, 19(12), 1610-1618. https://doi.org/10.1038/nn.4407

Vancouver

Sivadasan R, Hornburg D, Drepper C, Frank N, Jablonka S, Hansel A o.a. C9ORF72 interaction with cofilin modulates actin dynamics in motor neurons. Nature Neuroscience. 2016 dec.;19(12):1610-1618. https://doi.org/10.1038/nn.4407

Author

Sivadasan, Rajeeve ; Hornburg, Daniel ; Drepper, Carsten ; Frank, Nicolas ; Jablonka, Sibylle ; Hansel, Anna ; Lojewski, Xenia ; Sterneckert, Jared ; Hermann, Andreas ; Shaw, Pamela J ; Ince, Paul G ; Mann, Matthias ; Meissner, Felix ; Sendtner, Michael. / C9ORF72 interaction with cofilin modulates actin dynamics in motor neurons. I: Nature Neuroscience. 2016 ; Bind 19, Nr. 12. s. 1610-1618.

Bibtex

@article{6666341a78404057a91987f2332a87ed,
title = "C9ORF72 interaction with cofilin modulates actin dynamics in motor neurons",
abstract = "Intronic hexanucleotide expansions in C9ORF72 are common in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia, but it is unknown whether loss of function, toxicity by the expanded RNA or dipeptides from non-ATG-initiated translation are responsible for the pathophysiology. We determined the interactome of C9ORF72 in motor neurons and found that C9ORF72 was present in a complex with cofilin and other actin binding proteins. Phosphorylation of cofilin was enhanced in C9ORF72-depleted motor neurons, in patient-derived lymphoblastoid cells, induced pluripotent stem cell-derived motor neurons and post-mortem brain samples from ALS patients. C9ORF72 modulates the activity of the small GTPases Arf6 and Rac1, resulting in enhanced activity of LIM-kinases 1 and 2 (LIMK1/2). This results in reduced axonal actin dynamics in C9ORF72-depleted motor neurons. Dominant negative Arf6 rescues this defect, suggesting that C9ORF72 acts as a modulator of small GTPases in a pathway that regulates axonal actin dynamics.",
keywords = "Actin Depolymerizing Factors, Actins, Amyotrophic Lateral Sclerosis, Animals, Brain, DNA Repeat Expansion, Frontotemporal Dementia, Guanine Nucleotide Exchange Factors, Humans, Induced Pluripotent Stem Cells, Mice, Microfilament Proteins, Motor Neurons, Proteins, Journal Article",
author = "Rajeeve Sivadasan and Daniel Hornburg and Carsten Drepper and Nicolas Frank and Sibylle Jablonka and Anna Hansel and Xenia Lojewski and Jared Sterneckert and Andreas Hermann and Shaw, {Pamela J} and Ince, {Paul G} and Matthias Mann and Felix Meissner and Michael Sendtner",
year = "2016",
month = dec,
doi = "10.1038/nn.4407",
language = "English",
volume = "19",
pages = "1610--1618",
journal = "Nature Neuroscience",
issn = "1097-6256",
publisher = "nature publishing group",
number = "12",

}

RIS

TY - JOUR

T1 - C9ORF72 interaction with cofilin modulates actin dynamics in motor neurons

AU - Sivadasan, Rajeeve

AU - Hornburg, Daniel

AU - Drepper, Carsten

AU - Frank, Nicolas

AU - Jablonka, Sibylle

AU - Hansel, Anna

AU - Lojewski, Xenia

AU - Sterneckert, Jared

AU - Hermann, Andreas

AU - Shaw, Pamela J

AU - Ince, Paul G

AU - Mann, Matthias

AU - Meissner, Felix

AU - Sendtner, Michael

PY - 2016/12

Y1 - 2016/12

N2 - Intronic hexanucleotide expansions in C9ORF72 are common in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia, but it is unknown whether loss of function, toxicity by the expanded RNA or dipeptides from non-ATG-initiated translation are responsible for the pathophysiology. We determined the interactome of C9ORF72 in motor neurons and found that C9ORF72 was present in a complex with cofilin and other actin binding proteins. Phosphorylation of cofilin was enhanced in C9ORF72-depleted motor neurons, in patient-derived lymphoblastoid cells, induced pluripotent stem cell-derived motor neurons and post-mortem brain samples from ALS patients. C9ORF72 modulates the activity of the small GTPases Arf6 and Rac1, resulting in enhanced activity of LIM-kinases 1 and 2 (LIMK1/2). This results in reduced axonal actin dynamics in C9ORF72-depleted motor neurons. Dominant negative Arf6 rescues this defect, suggesting that C9ORF72 acts as a modulator of small GTPases in a pathway that regulates axonal actin dynamics.

AB - Intronic hexanucleotide expansions in C9ORF72 are common in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia, but it is unknown whether loss of function, toxicity by the expanded RNA or dipeptides from non-ATG-initiated translation are responsible for the pathophysiology. We determined the interactome of C9ORF72 in motor neurons and found that C9ORF72 was present in a complex with cofilin and other actin binding proteins. Phosphorylation of cofilin was enhanced in C9ORF72-depleted motor neurons, in patient-derived lymphoblastoid cells, induced pluripotent stem cell-derived motor neurons and post-mortem brain samples from ALS patients. C9ORF72 modulates the activity of the small GTPases Arf6 and Rac1, resulting in enhanced activity of LIM-kinases 1 and 2 (LIMK1/2). This results in reduced axonal actin dynamics in C9ORF72-depleted motor neurons. Dominant negative Arf6 rescues this defect, suggesting that C9ORF72 acts as a modulator of small GTPases in a pathway that regulates axonal actin dynamics.

KW - Actin Depolymerizing Factors

KW - Actins

KW - Amyotrophic Lateral Sclerosis

KW - Animals

KW - Brain

KW - DNA Repeat Expansion

KW - Frontotemporal Dementia

KW - Guanine Nucleotide Exchange Factors

KW - Humans

KW - Induced Pluripotent Stem Cells

KW - Mice

KW - Microfilament Proteins

KW - Motor Neurons

KW - Proteins

KW - Journal Article

U2 - 10.1038/nn.4407

DO - 10.1038/nn.4407

M3 - Journal article

C2 - 27723745

VL - 19

SP - 1610

EP - 1618

JO - Nature Neuroscience

JF - Nature Neuroscience

SN - 1097-6256

IS - 12

ER -

ID: 184324278