ATP induces post-synaptic gene expressions in vertebrate skeletal neuromuscular junctions.
In vertebrate neuromuscular junctions (nmjs), adenosine 5'-triphosphate (ATP) is stored at the motor nerve terminals and is co-released with acetylcholine during neural stimulation. Several lines of evidence suggest that the synaptic ATP can act as a synapse-organizing factor at the nmjs, mediated by metabotropic P2Y(1) receptors. P2Y(1) receptor mRNAs in chicken and rat muscles are low in embryo but increases markedly in the adult, and decreased after denervation. The P2Y(1) receptor protein is restricted to the nmjs and co-localized with AChRs in adult muscles. The activation of P2Y(1) receptor by adenine nucleotides in cultured chick myotubes stimulated the accumulation of inositol phosphates, intracellular Ca(2+) mobilization, protein kinase C activity and phosphorylation of extracellular signal-regulated kinases. The receptor activation led to an increase in the expression of transcripts encoding AChE catalytic subunit and AChR subunits. The ATP-induced post-synaptic gene expression is possibly mediated by the activation of signaling cascades of mitogen-activated protein kinase. Therefore, a model is being proposed here that the synaptic ATP has a role of synergy with other regulatory signals, such as neuregulin, which act via their post-synaptic receptors to activate second signaling molecules locally to enhance the transcription of AChR/AChE genes specifically in the adjacent sub-synaptic nuclei during the formation and, especially, the maintenance of post-synaptic specializations at the nmjs.
Tsim
Karl W K
KW
Departments of Biology and Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Clear Water Bay Road, Hong Kong, China. BOTSIM@UST.HK
Choi
Roy C Y
RC
Siow
Nina L
NL
Cheng
Anthony W M
AW
Ling
Karen K Y
KK
Jiang
Joy X S
JX
Tung
Edmund K K
EK
Lee
Henry H C
HH
Xie
Qun H
QH
Simon
Joseph
J
Barnard
Eric A
EA
D000255:Adenosine Triphosphate / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects / Q000235:genetics / Q000378:metabolism
D000255:Adenosine Triphosphate