Phactr1 regulates Slack (KCNT1) channels via protein phosphatase 1 (PP1)

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F20%3A00521727" target="_blank" >RIV/68378050:_____/20:00521727 - isvavai.cz</a>

Result on the web

<a href="https://faseb.onlinelibrary.wiley.com/doi/full/10.1096/fj.201902366R" target="_blank" >https://faseb.onlinelibrary.wiley.com/doi/full/10.1096/fj.201902366R</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1096/fj.201902366R" target="_blank" >10.1096/fj.201902366R</a>

Result language

angličtina

Original language name

Phactr1 regulates Slack (KCNT1) channels via protein phosphatase 1 (PP1)

Original language description

The Slack (KCNT1) gene encodes sodium-activated potassium channels that are abundantly expressed in the central nervous system. Human mutations alter the function of Slack channels, resulting in epilepsy and intellectual disability. Most of the disease-causing mutations are located in the extended cytoplasmic C-terminus of Slack channels and result in increased Slack current. Previous experiments have shown that the C-terminus of Slack channels binds a number of cytoplasmic signaling proteins. One of these is Phactr1, an actin-binding protein that recruits protein phosphatase 1 (PP1) to certain phosphoprotein substrates. Using co-immunoprecipitation, we found that Phactr1 is required to link the channels to actin. Using patch clamp recordings, we found that co-expression of Phactr1 with wild-type Slack channels reduces the current amplitude but has no effect on Slack channels in which a conserved PKC phosphorylation site (S407) that regulates the current amplitude has been mutated. Furthermore, a Phactr1 mutant that disrupts the binding of PP1 but not that of actin fails to alter Slack currents. Our data suggest that Phactr1 regulates the Slack by linking PP1 to the channel. Targeting Slack-Phactr1 interactions may therefore be helpful in developing the novel therapies for brain disorders associated with the malfunction of Slack channels.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10601 - Cell biology

Project

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Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2020

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

FASEB Journal

ISSN

0892-6638

e-ISSN

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Volume of the periodical

34

Issue of the periodical within the volume

1

Country of publishing house

US - UNITED STATES

Number of pages

11

Pages from-to

1591-1601

UT code for WoS article

000507308900105

EID of the result in the Scopus database

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