The ion transporter nkcc1 links cell volume to cell mass regulation by suppressing mtorc1

Demian, Wael L.; Persaud, Avinash; Jiang, Chong; Coyaud, Etienne-Marie; Liu, Shixuan; Kapus, Andras; Kafri, Ran; Raught, Brian; Rotin, Daniela

Document type :

Article dans une revue scientifique: Article original

DOI :

10.1016/j.celrep.2019.04.034

PMID :

31067471

Permalink :

http://hdl.handle.net/20.500.12210/74988

Title :

The ion transporter nkcc1 links cell volume to cell mass regulation by suppressing mtorc1

Author(s) :

Demian, Wael L. [Auteur]
Persaud, Avinash [Auteur]
Jiang, Chong [Auteur]
Coyaud, Etienne-Marie [Auteur]
Liu, Shixuan [Auteur]
Kapus, Andras [Auteur]
Kafri, Ran [Auteur]
Raught, Brian [Auteur]
Rotin, Daniela [Auteur]

Journal title :

Cell Reports

Abbreviated title :

Cell Reports

Volume number :

Pages :

Publication date :

2019-05-07

ISSN :

2211-1247

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

mTORC1 regulates cellular growth and is activated by growth factors and by essential amino acids such as Leu. Leu enters cells via the Leu transporter LAT1-4F2hc (LAT1). Here we show that the Na(+)/K(+)/2Cl(-) cotransporter ...
Show more >mTORC1 regulates cellular growth and is activated by growth factors and by essential amino acids such as Leu. Leu enters cells via the Leu transporter LAT1-4F2hc (LAT1). Here we show that the Na(+)/K(+)/2Cl(-) cotransporter NKCC1 (SLC12A2), a known regulator of cell volume, is present in complex with LAT1. We further show that NKCC1 depletion or deletion enhances LAT1 activity, as well as activation of Akt and Erk, leading to activation of mTORC1 in cells, colonic organoids, and mouse colon. Moreover, NKCC1 depletion reduces intracellular Na(+) concentration and cell volume (size) and mass and stimulates cell proliferation. NKCC1, therefore, suppresses mTORC1 by inhibiting its key activating signaling pathways. Importantly, by linking ion transport and cell volume regulation to mTORC1 function, NKCC1 provides a long-sought link connecting cell volume (size) to cell mass regulation.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

INSERM
Université de Lille

Collections :

Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192

Submission date :

2022-06-15T13:57:43Z

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