scholarly journals PAK1 and CtBP1 Regulate the Coupling of Neuronal Activity to Muscle Chromatin and Gene Expression

2015 ◽  
Vol 35 (24) ◽  
pp. 4110-4120 ◽  
Author(s):  
Jean-Luc Thomas ◽  
Vincent Moncollin ◽  
Aymeric Ravel-Chapuis ◽  
Carmen Valente ◽  
Daniela Corda ◽  
...  

Acetylcholine receptor (AChR) expression in innervated muscle is limited to the synaptic region. Neuron-induced electrical activity participates in this compartmentalization by promoting the repression of AChR expression in the extrasynaptic regions. Here, we show that the corepressor CtBP1 (C-terminal binding protein 1) is present on the myogenin promoter together with repressive histone marks. shRNA-mediated downregulation of CtBP1 expression is sufficient to derepress myogenin and AChR expression in innervated muscle. Upon denervation, CtBP1 is displaced from the myogenin promoter and relocates to the cytoplasm, while repressive histone marks are replaced by activating ones concomitantly to the activation of myogenin expression. We also observed that upon denervation the p21-activated kinase 1 (PAK1) expression is upregulated, suggesting that phosphorylation by PAK1 may be involved in the relocation of CtBP1. Indeed, preventing CtBP1 Ser158 phosphorylation induces CtBP1 accumulation in the nuclei and abrogates the activation of myogenin and AChR expression. Altogether, these findings reveal a molecular mechanism to account for the coordinated control of chromatin modifications and muscle gene expression by presynaptic neurons via a PAK1/CtBP1 pathway.

Author(s):  
Lúcio Flávio Macedo Mota ◽  
Cristina Moreira Bonafé ◽  
Pâmela Almeida Alexandre ◽  
Miguel Henrique Santana ◽  
Francisco José Novais ◽  
...  

2005 ◽  
Vol 280 (10) ◽  
pp. 9719-9727 ◽  
Author(s):  
Yan Liu ◽  
Sanjay Sinha ◽  
Oliver G. McDonald ◽  
Yueting Shang ◽  
Mark H. Hoofnagle ◽  
...  

2007 ◽  
Vol 27 (13) ◽  
pp. 5040-5046 ◽  
Author(s):  
Alexander Jaworski ◽  
Cynthia L. Smith ◽  
Steven J. Burden

ABSTRACT The mRNAs encoding postsynaptic components at the neuromuscular junction are concentrated in the synaptic region of muscle fibers. Accumulation of these RNAs in the synaptic region is mediated, at least in part, by selective transcription of the corresponding genes in synaptic myofiber nuclei. The transcriptional mechanisms that are responsible for synapse-specific gene expression are largely unknown, but an Ets site in the promoter regions of acetylcholine receptor (AChR) subunit genes and other “synaptic” genes is required for synapse-specific transcription. The Ets domain transcription factor GA-binding protein (GABP) has been implicated to mediate synapse-specific gene expression. Inactivation of GABPα, the DNA-binding subunit of GABP, leads to early embryonic lethality, preventing analysis of synapse formation in gabpα mutant mice. To study the role of GABP at neuromuscular synapses, we conditionally inactivated gabpα in skeletal muscle and studied synaptic differentiation and muscle gene expression. Although expression of rb, a target of GABP, is elevated in muscle tissue deficient in GABPα, clustering of synaptic AChRs at synapses and synapse-specific gene expression are normal in these mice. These data indicate that GABP is dispensable for synapse-specific transcription and maintenance of normal AChR expression at synapses.


2004 ◽  
Vol 18 (3) ◽  
pp. 522-524 ◽  
Author(s):  
Takeshi Nikawa ◽  
Kazumi Ishidoh ◽  
Katsuya Hirasaka ◽  
Ibuki Ishihara ◽  
Madoka Ikemoto ◽  
...  

2010 ◽  
Vol 88 (4) ◽  
pp. 1349-1357 ◽  
Author(s):  
D. K. Walker ◽  
E. C. Titgemeyer ◽  
T. J. Baxa ◽  
K. Y. Chung ◽  
D. E. Johnson ◽  
...  

BMC Genetics ◽  
2018 ◽  
Vol 19 (1) ◽  
Author(s):  
I-Hsuan Lin ◽  
Junn-Liang Chang ◽  
Kate Hua ◽  
Wan-Chen Huang ◽  
Ming-Ta Hsu ◽  
...  

Author(s):  
Ferdinand von Walden ◽  
Rodrigo Fernandez-Gonzalo ◽  
Jessica Maria Norrbom ◽  
Eric B. Emanuelsson ◽  
Vandre C. Figueiredo ◽  
...  

Mitochondrial derived peptides (MDPs) humanin (HN) and mitochondrial open reading frame of the 12S rRNA-c (MOTS-c) are involved in cell survival, suppression of apoptosis and metabolism. Circulating levels of MDPs are altered in chronic diseases such as diabetes type 2 and chronic kidney disease. Whether acute resistance (RE) or endurance (EE) exercise modulates circulating levels of HN and MOTS-c in humans is unknown. Following familiarization, subjects were randomized to EE (n=10, 45 min cycling at 70% of estimated VO2max), RE (n=10, 4 sets x 7RM, leg press and knee extension), or control (CON, n=10). Skeletal muscle biopsies and blood samples were collected before and at 30 minutes and 3 hours following exercise. Plasma concentration of HN and MOTS-c, skeletal muscle MOTS-c as well as gene expression of exercise related genes were analyzed. Acute EE and RE promoted changes in skeletal muscle gene expression typically seen in response to each exercise modality (c-Myc, 45S pre-rRNA, PGC-1α-total and PGC-1α-ex1b). At rest, circulating levels of HN were positively correlated to MOTS-c levels and age. Plasma levels of MDPs were not correlated to fitness outcomes (VO2max, leg strength or muscle mitochondrial (mt) DNA copy number). Circulating levels of HN were significantly elevated by acute EE but not RE. MOTS-C levels showed a trend to increase after EE. These results indicate that plasma MDP levels are not related to fitness status but that acute EE increases circulating levels of MDPs, in particular HN.


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