Luminal STIM1 Mutants that Cause Tubular Aggregate Myopathy Promote Autophagic Processes

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388971%3A_____%2F20%3A00533047" target="_blank" >RIV/61388971:_____/20:00533047 - isvavai.cz</a>

Result on the web

<a href="https://www.mdpi.com/1422-0067/21/12/4410" target="_blank" >https://www.mdpi.com/1422-0067/21/12/4410</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/ijms21124410" target="_blank" >10.3390/ijms21124410</a>

Result language

angličtina

Original language name

Luminal STIM1 Mutants that Cause Tubular Aggregate Myopathy Promote Autophagic Processes

Original language description

Stromal interaction molecule 1 (STIM1) is a ubiquitously expressed Ca(2+)sensor protein that induces permeation of Orai Ca(2+)channels upon endoplasmic reticulum Ca2+-store depletion. A drop in luminal Ca(2+)causes partial unfolding of the N-terminal STIM1 domains and thus initial STIM1 activation. We compared the STIM1 structure upon Ca(2+)depletion from our molecular dynamics (MD) simulations with a recent 2D NMR structure. Simulation- and structure-based results showed unfolding of two alpha-helices in the canonical and in the non-canonical EF-hand. Further, we structurally and functionally evaluated mutations in the non-canonical EF-hand that have been shown to cause tubular aggregate myopathy. We found these mutations to cause full constitutive activation of Ca2+-release-activated Ca(2+)currents (I-CRAC) and to promote autophagic processes. Specifically, heterologously expressed STIM1 mutations in the non-canonical EF-hand promoted translocation of the autophagy transcription factors microphthalmia-associated transcription factor (MITF) and transcription factor EB (TFEB) into the nucleus. These STIM1 mutations additionally stimulated an enhanced production of autophagosomes. In summary, mutations in STIM1 that cause structural unfolding promoted Ca(2+)down-stream activation of autophagic processes.

Czech name

—

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

—

OECD FORD branch

10608 - Biochemistry and molecular biology

Project

<a href="/en/project/GJ19-20728Y" target="_blank" >GJ19-20728Y: Modeling activation of human calcium release-activated channels.</a><br>

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

International Journal of Molecular Sciences

ISSN

1422-0067

e-ISSN

—

Volume of the periodical

21

Issue of the periodical within the volume

12

Country of publishing house

CH - SWITZERLAND

Number of pages

15

Pages from-to

4410

UT code for WoS article

000550162400001

EID of the result in the Scopus database

2-s2.0-85087010833