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Dynein links engulfment and execution of apoptosis via CED-4/Apaf1 in C. elegans

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Standard

Dynein links engulfment and execution of apoptosis via CED-4/Apaf1 in C. elegans. / Harders, Rikke Hindsgaul; Morthorst, Tine Hørning; Lande, Anna Dippel et al.

I: Cell Death and Disease, Bind 9, Nr. 10, 1012, 01.10.2018.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

Harvard

Harders, RH, Morthorst, TH, Lande, AD, Hesselager, MO, Mandrup, OA, Bendixen, E, Stensballe, A & Olsen, A 2018, 'Dynein links engulfment and execution of apoptosis via CED-4/Apaf1 in C. elegans', Cell Death and Disease, bind 9, nr. 10, 1012. https://doi.org/10.1038/s41419-018-1067-y

APA

Harders, R. H., Morthorst, T. H., Lande, A. D., Hesselager, M. O., Mandrup, O. A., Bendixen, E., Stensballe, A., & Olsen, A. (2018). Dynein links engulfment and execution of apoptosis via CED-4/Apaf1 in C. elegans. Cell Death and Disease, 9(10), [1012]. https://doi.org/10.1038/s41419-018-1067-y

CBE

Harders RH, Morthorst TH, Lande AD, Hesselager MO, Mandrup OA, Bendixen E, Stensballe A, Olsen A. 2018. Dynein links engulfment and execution of apoptosis via CED-4/Apaf1 in C. elegans. Cell Death and Disease. 9(10):Article 1012. https://doi.org/10.1038/s41419-018-1067-y

MLA

Vancouver

Harders RH, Morthorst TH, Lande AD, Hesselager MO, Mandrup OA, Bendixen E et al. Dynein links engulfment and execution of apoptosis via CED-4/Apaf1 in C. elegans. Cell Death and Disease. 2018 okt. 1;9(10):1012. doi: 10.1038/s41419-018-1067-y

Author

Harders, Rikke Hindsgaul ; Morthorst, Tine Hørning ; Lande, Anna Dippel et al. / Dynein links engulfment and execution of apoptosis via CED-4/Apaf1 in C. elegans. I: Cell Death and Disease. 2018 ; Bind 9, Nr. 10.

Bibtex

@article{76e7a337c97140be92e62d89b4d76e22,
title = "Dynein links engulfment and execution of apoptosis via CED-4/Apaf1 in C. elegans",
abstract = "Apoptosis ensures removal of damaged cells and helps shape organs during development by removing excessive cells. To prevent the intracellular content of the apoptotic cells causing damage to surrounding cells, apoptotic cells are quickly cleared by engulfment. Tight regulation of apoptosis and engulfment is needed to prevent several pathologies such as cancer, neurodegenerative and autoimmune diseases. There is increasing evidence that the engulfment machinery can regulate the execution of apoptosis. However, the underlying molecular mechanisms are poorly understood. We show that dynein mediates cell non-autonomous cross-talk between the engulfment and apoptotic programs in the Caenorhabditis elegans germline. Dynein is an ATP-powered microtubule-based molecular motor, built from several subunits. Dynein has many diverse functions including transport of cargo around the cell. We show that both dynein light chain 1 (DLC-1) and dynein heavy chain 1 (DHC-1) localize to the nuclear membrane inside apoptotic germ cells in C. elegans. Strikingly, lack of either DLC-1 or DHC-1 at the nuclear membrane inhibits physiological apoptosis specifically in mutants defective in engulfment. This suggests that a cell fate determining dialogue takes place between engulfing somatic sheath cells and apoptotic germ cells. The underlying mechanism involves the core apoptotic protein CED-4/Apaf1, as we find that DLC-1 and the engulfment protein CED-6/GULP are required for the localization of CED-4 to the nuclear membrane of germ cells. A better understanding of the communication between the engulfment machinery and the apoptotic program is essential for identifying novel therapeutic targets in diseases caused by inappropriate engulfment or apoptosis.",
author = "Harders, {Rikke Hindsgaul} and Morthorst, {Tine H{\o}rning} and Lande, {Anna Dippel} and Hesselager, {Marianne Overgaard} and Mandrup, {Ole Aalund} and Em{\o}ke Bendixen and Allan Stensballe and Anders Olsen",
year = "2018",
month = oct,
day = "1",
doi = "10.1038/s41419-018-1067-y",
language = "English",
volume = "9",
journal = "Cell Death & Disease",
issn = "2041-4889",
publisher = "Nature Publishing Group",
number = "10",

}

RIS

TY - JOUR

T1 - Dynein links engulfment and execution of apoptosis via CED-4/Apaf1 in C. elegans

AU - Harders, Rikke Hindsgaul

AU - Morthorst, Tine Hørning

AU - Lande, Anna Dippel

AU - Hesselager, Marianne Overgaard

AU - Mandrup, Ole Aalund

AU - Bendixen, Emøke

AU - Stensballe, Allan

AU - Olsen, Anders

PY - 2018/10/1

Y1 - 2018/10/1

N2 - Apoptosis ensures removal of damaged cells and helps shape organs during development by removing excessive cells. To prevent the intracellular content of the apoptotic cells causing damage to surrounding cells, apoptotic cells are quickly cleared by engulfment. Tight regulation of apoptosis and engulfment is needed to prevent several pathologies such as cancer, neurodegenerative and autoimmune diseases. There is increasing evidence that the engulfment machinery can regulate the execution of apoptosis. However, the underlying molecular mechanisms are poorly understood. We show that dynein mediates cell non-autonomous cross-talk between the engulfment and apoptotic programs in the Caenorhabditis elegans germline. Dynein is an ATP-powered microtubule-based molecular motor, built from several subunits. Dynein has many diverse functions including transport of cargo around the cell. We show that both dynein light chain 1 (DLC-1) and dynein heavy chain 1 (DHC-1) localize to the nuclear membrane inside apoptotic germ cells in C. elegans. Strikingly, lack of either DLC-1 or DHC-1 at the nuclear membrane inhibits physiological apoptosis specifically in mutants defective in engulfment. This suggests that a cell fate determining dialogue takes place between engulfing somatic sheath cells and apoptotic germ cells. The underlying mechanism involves the core apoptotic protein CED-4/Apaf1, as we find that DLC-1 and the engulfment protein CED-6/GULP are required for the localization of CED-4 to the nuclear membrane of germ cells. A better understanding of the communication between the engulfment machinery and the apoptotic program is essential for identifying novel therapeutic targets in diseases caused by inappropriate engulfment or apoptosis.

AB - Apoptosis ensures removal of damaged cells and helps shape organs during development by removing excessive cells. To prevent the intracellular content of the apoptotic cells causing damage to surrounding cells, apoptotic cells are quickly cleared by engulfment. Tight regulation of apoptosis and engulfment is needed to prevent several pathologies such as cancer, neurodegenerative and autoimmune diseases. There is increasing evidence that the engulfment machinery can regulate the execution of apoptosis. However, the underlying molecular mechanisms are poorly understood. We show that dynein mediates cell non-autonomous cross-talk between the engulfment and apoptotic programs in the Caenorhabditis elegans germline. Dynein is an ATP-powered microtubule-based molecular motor, built from several subunits. Dynein has many diverse functions including transport of cargo around the cell. We show that both dynein light chain 1 (DLC-1) and dynein heavy chain 1 (DHC-1) localize to the nuclear membrane inside apoptotic germ cells in C. elegans. Strikingly, lack of either DLC-1 or DHC-1 at the nuclear membrane inhibits physiological apoptosis specifically in mutants defective in engulfment. This suggests that a cell fate determining dialogue takes place between engulfing somatic sheath cells and apoptotic germ cells. The underlying mechanism involves the core apoptotic protein CED-4/Apaf1, as we find that DLC-1 and the engulfment protein CED-6/GULP are required for the localization of CED-4 to the nuclear membrane of germ cells. A better understanding of the communication between the engulfment machinery and the apoptotic program is essential for identifying novel therapeutic targets in diseases caused by inappropriate engulfment or apoptosis.

UR - http://www.scopus.com/inward/record.url?scp=85054082110&partnerID=8YFLogxK

U2 - 10.1038/s41419-018-1067-y

DO - 10.1038/s41419-018-1067-y

M3 - Journal article

C2 - 30262881

AN - SCOPUS:85054082110

VL - 9

JO - Cell Death & Disease

JF - Cell Death & Disease

SN - 2041-4889

IS - 10

M1 - 1012

ER -