Class I HDACs control a JIP1-dependent pathway for kinesin-microtubule binding in cardiomyocytes.
J Mol Cell Cardiol
; 112: 74-82, 2017 11.
Article
in En
| MEDLINE
| ID: mdl-28886967
ABSTRACT
Class I histone deacetylase (HDAC) inhibitors block hypertrophy and fibrosis of the heart by suppressing pathological signaling and gene expression programs in cardiac myocytes and fibroblasts. The impact of HDAC inhibition in unstressed cardiac cells remains poorly understood. Here, we demonstrate that treatment of cultured cardiomyocytes with small molecule HDAC inhibitors leads to dramatic induction of c-Jun amino-terminal kinase (JNK)-interacting protein-1 (JIP1) mRNA and protein expression. In contrast to prior findings, elevated levels of endogenous JIP1 in cardiomyocytes failed to significantly alter JNK signaling or cardiomyocyte hypertrophy. Instead, HDAC inhibitor-mediated induction of JIP1 was required to stimulate expression of the kinesin heavy chain family member, KIF5A. We provide evidence for an HDAC-dependent regulatory circuit that promotes formation of JIP1KIF5Amicrotubule complexes that regulate intracellular transport of cargo such as autophagosomes. These findings define a novel role for class I HDACs in the control of the JIP1/kinesin axis in cardiomyocytes, and suggest that HDAC inhibitors could be used to alter microtubule transport in the heart.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Kinesins
/
Myocytes, Cardiac
/
Adaptor Proteins, Signal Transducing
/
Histone Deacetylases
/
Microtubules
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
J Mol Cell Cardiol
Year:
2017
Document type:
Article
Affiliation country:
Estados Unidos