Cardiac-specific deletion of protein phosphatase 1β promotes increased myofilament protein phosphorylation and contractile alterations

Journal of Molecular and Cellular Cardiology
Ruijie LiuJeffery D Molkentin

Abstract

There are 3 protein phosphatase 1 (PP1) catalytic isoforms (α, β and γ) encoded within the mammalian genome. These 3 gene products share ~90% amino acid homology within their catalytic domains but each has unique N- and C-termini that likely underlie distinctive subcellular localization or functionality. In this study, we assessed the effect associated with the loss of each PP1 isoform in the heart using a conditional Cre-loxP targeting approach in mice. Ppp1ca-loxP, Ppp1cb-loxP and Ppp1cc-loxP alleles were crossed with either an Nkx2.5-Cre knock-in containing allele for early embryonic deletion or a tamoxifen inducible α-myosin heavy chain (αMHC)-MerCreMer transgene for adult and cardiac-specific deletion. We determined that while deletion of Ppp1ca (PP1α) or Ppp1cc (PP1γ) had little effect on the whole heart, deletion of Ppp1cb (PP1β) resulted in concentric remodeling of the heart, interstitial fibrosis and contractile dysregulation, using either the embryonic or adult-specific Cre-expressing alleles. However, myocytes isolated from Ppp1cb deleted hearts surprisingly showed enhanced contractility. Mechanistically we found that deletion of any of the 3 PP1 gene-encoding isoforms had no effect on phosphorylation of phospholamba...Continue Reading

References

Jan 10, 2002·Genesis : the Journal of Genetics and Development·K A MosesR J Schwartz
May 25, 2002·Molecular and Cellular Biology·Andrew N CarrEvangelia G Kranias
Sep 25, 2002·The Journal of Biological Chemistry·Ryan T Terry-LorenzoShirish Shenolikar
Jan 13, 2004·Physiological Reviews·Hugo Ceulemans, Mathieu Bollen
Mar 17, 2005·Cardiovascular Research·Joanne LaylandAjay M Shah
Jun 25, 2005·Cardiovascular Research·Uwe KirchheferJoachim Neumann
Jul 15, 2005·American Journal of Physiology. Heart and Circulatory Physiology·Daniel BurkhoffHiroyuki Suga
Apr 22, 2006·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Michio YamadaMasunori Matsuzaki
May 3, 2006·Proceedings of the National Academy of Sciences of the United States of America·Minoru SatohJames K Liao
Nov 1, 2006·Proceedings of the National Academy of Sciences of the United States of America·Sakthivel SadayappanJeffrey Robbins
Sep 22, 2007·The Journal of Clinical Investigation·Osamu SeguchiMasafumi Kitakaze
Jun 2, 2009·Journal of Molecular and Cellular Cardiology·Persoulla NicolaouEvangelia G Kranias
Dec 29, 2009·The Journal of Biological Chemistry·Marjorie MailletJeffery D Molkentin
Mar 23, 2010·Nature Structural & Molecular Biology·Michael J RagusaWolfgang Peti
Apr 20, 2010·Trends in Biochemical Sciences·Mathieu BollenMonique Beullens
Nov 26, 2010·The Journal of Clinical Investigation·Thomas Eschenhagen
Feb 25, 2011·Archives of Biochemistry and Biophysics·Sarah B Scruggs, R John Solaro
May 13, 2011·Biochemistry·Andrew V LeKimberly L Dodge-Kafka
Mar 29, 2012·Cardiology Research and Practice·Stephen J Huang, Anthony S McLean
May 2, 2012·Circulation·Rick A Nishimura, Blase A Carabello
Jun 5, 2012·Journal of Proteomics·Kumar KotloRobert S Danziger
Jan 19, 2013·Circulation Research·R John SolaroTomoyoshi Kobayashi
Jun 12, 2013·Biophysical Journal·Árpád KarsaiSamantha P Harris
Aug 24, 2013·Trends in Cardiovascular Medicine·Farah SheikhJu Chen
Sep 21, 2013·Journal of Molecular and Cellular Cardiology·Jordi HeijmanDobromir Dobrev
Jan 21, 2014·Pflügers Archiv : European journal of physiology·Carl W TongPaola C Rosas
Jan 2, 2015·Circulation Research·Richard L MossJ Carter Ralphe
Jan 17, 2015·Journal of the American College of Cardiology·David Y ChiangArjen Scholten
Mar 6, 2015·Circulation. Heart Failure·Paola C RosasCarl W Tong

❮ Previous
Next ❯

Citations

Dec 1, 2015·Frontiers in Pharmacology·Silvio WeberAli El-Armouche
Sep 3, 2016·Journal of Molecular and Cellular Cardiology·Dmitry Terentyev, Shanna Hamilton
Oct 11, 2016·Journal of Molecular and Cellular Cardiology·Ilka Lorenzen-SchmidtW Glen Pyle
May 27, 2016·Circulation Research·Ruijie LiuJeffery D Molkentin
Feb 10, 2019·Biomolecules·Margarida Moura, Carlos Conde
Nov 28, 2019·Nature·Ronald J VagnozziJeffery D Molkentin
Sep 12, 2017·The Journal of Clinical Investigation·Hadi KhalilJeffery D Molkentin
Jun 10, 2017·Basic Research in Cardiology·Stefanie Meyer-RoxlauAli El-Armouche
Oct 16, 2016·Journal of Molecular and Cellular Cardiology·Audrey N ChangJames T Stull
Oct 8, 2021·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Masaaki ItoKaoru Dohi

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cardiac Remodeling

Cardiac remodeling in response to a myocardial infarction is characterized by progressive ventricular dilatation, cardiac hypertrophy, fibrosis, and deterioration of cardiac performance. Discover the latest research on Cardiac Remodeling here.

Cardiomyopathy

Cardiomyopathy is a disease of the heart muscle, that can lead to muscular or electrical dysfunction of the heart. It is often an irreversible disease that is associated with a poor prognosis. There are different causes and classifications of cardiomyopathies. Here are the latest discoveries pertaining to this disease.

Cardiomegaly

Cardiomegaly, known as an enlarged heart, is a multifactorial disease with different pathophysiological mechanisms. Hypertension, pregnancy, exercise-induced and idiopathic causes are some mechanisms of cardiomegaly. Discover the latest research of cardiomegaly here.

Aphasia

Aphasia affects the ability to process language, including formulation and comprehension of language and speech, as well as the ability to read or write. Here is the latest research on aphasia.