Expression of cAMP-responsive element binding proteins (CREBs) in fast- and slow-twitch muscles: A signaling pathway to account for the synaptic expression of collagen-tailed subunit (ColQ) of acetylcholinesterase at the rat neuromuscular junction.
The gene encoding the collagen-tailed subunit (ColQ) of acetylcholinesterase (AChE) contains two distinct promoters that drive the production of two ColQ mRNAs, ColQ-1 and ColQ-1a, in slow- and fast-twitch muscles, respectively. ColQ-1a is expressed at the neuromuscular junction (NMJ) in fast-twitch muscle, and this expression depends on trophic factors supplied by motor neurons signaling via a cAMP-dependent pathway in muscle. To further elucidate the molecular basis of ColQ-1a's synaptic expression, here we investigated the expression and localization of cAMP-responsive element binding protein (CREB) at the synaptic and extra-synaptic regions of fast- and slow-twitch muscles from adult rats. The total amount of active, phosphorylated CREB (P-CREB) present in slow-twitch soleus muscle was higher than that in fast-twitch tibialis muscle, but P-CREB was predominantly expressed in the fast-twitch muscle at NMJs. In contrast, P-CREB was detected in both synaptic and extra-synaptic regions of slow-twitch muscle. These results reveal, for the first time, the differential distribution of P-CREB in fast- and slow-twitch muscles, which might support the crucial role of cAMP-dependent signaling in controlling the synapse-specific expression of ColQ-1a in fast-twitch muscles.
T10 T11 T12 T13 T14 T15 T16 T17 T18 T19 T1 T20 T21 T22 T23 T24 T25 T26 T2 T3 T4 T5 T6 T7 T8 T9
GENE-Y GENE-Y GENE-Y GENE-Y GENE-N GENE-Y GENE-N GENE-N GENE-N GENE-Y CHEMICAL GENE-N GENE-N GENE-N GENE-Y GENE-Y GENE-Y GENE-N CHEMICAL CHEMICAL CHEMICAL GENE-N GENE-Y GENE-Y GENE-Y GENE-Y
collagen-tailed subunit ColQ-1a ColQ ColQ-1a's cAMP-responsive element binding protein acetylcholinesterase CREB phosphorylated CREB P-CREB AChE cAMP P-CREB P-CREB cAMP-responsive element binding proteins collagen-tailed subunit ColQ acetylcholinesterase CREBs cAMP cAMP cAMP P-CREB ColQ-1a ColQ ColQ-1 ColQ-1a