TY - JOUR
T1 - Cysteine Rich Intestinal Protein 2 is a copper-responsive regulator of skeletal muscle differentiation and metal homeostasis
AU - Verdejo-Torres, Odette
AU - Klein, David C.
AU - Novoa-Aponte, Lorena
AU - Carrazco-Carrillo, Jaime
AU - Bonilla-Pinto, Denzel
AU - Rivera, Antonio
AU - Bakhshian, Arpie
AU - Fitisemanu, Fa alataitaua M.
AU - Jiménez-González, Martha L.
AU - Flinn, Lyra
AU - Pezacki, Aidan T.
AU - Lanzirotti, Antonio
AU - Frade, Luis Antonio Ortiz
AU - Chang, Christopher J.
AU - Navea, Juan G.
AU - Blaby-Haas, Crysten E.
AU - Hainer, Sarah J.
AU - PadillaBenavides, Teresita
N1 - Publisher Copyright:
© 2024 Verdejo-Torres et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2024/12/5
Y1 - 2024/12/5
N2 - Copper (Cu) is essential for respiration, neurotransmitter synthesis, oxidative stress response, and transcription regulation, with imbalances leading to neurological, cognitive, and muscular disorders. Here we show the role of a novel Cu-binding protein (Cu-BP) in mammalian transcriptional regulation, specifically on skeletal muscle differentiation using murine primary myoblasts. Utilizing synchrotron X-ray fluorescence-mass spectrometry, we identified murine cysteine-rich intestinal protein 2 (mCrip2) as a key Cu-BP abundant in both nuclear and cytosolic fractions. mCrip2 binds two to four Cu+ ions with high affinity and presents limited redox potential. CRISPR/Cas9-mediated deletion of mCrip2 impaired myogenesis, likely due to Cu accumulation in cells. CUT&RUN and transcriptome analyses revealed its association with gene promoters, including MyoD1 and metallothioneins, suggesting a novel Cu-responsive regulatory role for mCrip2. Our work describes the significance of mCrip2 in skeletal muscle differentiation and metal homeostasis, expanding understanding of the Cu-network in myoblasts.
AB - Copper (Cu) is essential for respiration, neurotransmitter synthesis, oxidative stress response, and transcription regulation, with imbalances leading to neurological, cognitive, and muscular disorders. Here we show the role of a novel Cu-binding protein (Cu-BP) in mammalian transcriptional regulation, specifically on skeletal muscle differentiation using murine primary myoblasts. Utilizing synchrotron X-ray fluorescence-mass spectrometry, we identified murine cysteine-rich intestinal protein 2 (mCrip2) as a key Cu-BP abundant in both nuclear and cytosolic fractions. mCrip2 binds two to four Cu+ ions with high affinity and presents limited redox potential. CRISPR/Cas9-mediated deletion of mCrip2 impaired myogenesis, likely due to Cu accumulation in cells. CUT&RUN and transcriptome analyses revealed its association with gene promoters, including MyoD1 and metallothioneins, suggesting a novel Cu-responsive regulatory role for mCrip2. Our work describes the significance of mCrip2 in skeletal muscle differentiation and metal homeostasis, expanding understanding of the Cu-network in myoblasts.
UR - https://www.scopus.com/pages/publications/85211077981
UR - https://www.scopus.com/pages/publications/85211077981#tab=citedBy
U2 - 10.1371/journal.pgen.1011495
DO - 10.1371/journal.pgen.1011495
M3 - Article
C2 - 39637238
AN - SCOPUS:85211077981
SN - 1553-7390
VL - 20
JO - PLoS genetics
JF - PLoS genetics
IS - 12
M1 - e1011495
ER -