title: 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.
abstract: 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.
authors.affiliation: Division of Life Science, State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Clear Water Bay Road, Hong Kong, SAR. roychoi@ust.hk
authors.forename: Roy C Y
authors.initials: RC
authors.lastname: Choi
authors.forename: Vicky P
authors.initials: VP
authors.lastname: Chen
authors.forename: Wilson K W
authors.initials: WK
authors.lastname: Luk
authors.forename: Amanda W Y
authors.initials: AW
authors.lastname: Yung
authors.forename: Alice H M
authors.initials: AH
authors.lastname: Ng
authors.forename: Tina T X
authors.initials: TT
authors.lastname: Dong
authors.forename: Karl W K
authors.initials: KW
authors.lastname: Tsim
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D003094:Collagen / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D058851:GPI-Linked Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D009046:Motor Neurons / Q000378:metabolism; D018656:Muscle Fibers, Fast-Twitch / Q000378:metabolism*; D018657:Muscle Fibers, Slow-Twitch / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000378:metabolism*; D010766:Phosphorylation; D021122:Protein Subunits; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D058851:GPI-Linked Proteins; D021122:Protein Subunits; D012333:RNA, Messenger; D003094:Collagen; D000110:Acetylcholinesterase; C548246:Ache protein, rat; C533412:ColQ protein, rat