Regulation of a transcript encoding the proline-rich membrane anchor of globular muscle acetylcholinesterase. The suppressive roles of myogenesis and innervating nerves.
The transcriptional regulation of proline-rich membrane anchor (PRiMA), an anchoring protein of tetrameric globular form acetylcholinesterase (G(4) AChE), was revealed in muscle during myogenic differentiation under the influence of innervation. During myotube formation of C2C12 cells, the expression of AChE(T) protein and the enzymatic activity were dramatically increased, but the level of G(4) AChE was relatively decreased. This G(4) AChE in C2C12 cells was specifically recognized by anti-PRiMA antibody, suggesting the association of this enzyme with PRiMA. Reverse transcription-PCR analysis revealed that the level of PRiMA mRNA was reduced during the myogenic differentiation of C2C12 cells. Overexpression of PRiMA in C2C12 myotubes significantly increased the production of G(4) AChE. The oligomerization of G(4) AChE, however, did not require the intracellular cytoplasmic tail of PRiMA. After overexpressing the muscle regulatory factors, myogenin and MyoD, the expressions of PRiMA and G(4) AChE in cultured myotubes were markedly reduced. In addition, calcitonin gene-related peptide, a known motor neuron-derived factor, and muscular activity were able to suppress PRiMA expression in muscle; the suppression was mediated by the phosphorylation of a cAMP-responsive element-binding protein. In accordance with the in vitro results, sciatic nerve denervation transiently increased the expression of PRiMA mRNA and decreased the phosphorylation of cAMP-responsive element-binding protein as well as its activator calcium/calmodulin-dependent protein kinase II in muscles. Our results suggest that the expression of PRiMA, as well as PRiMA-associated G(4) AChE, in muscle is suppressed by muscle regulatory factors, muscular activity, and nerve-derived trophic factor(s).
Xie
Heidi Q
HQ
Department of Biology and the Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Clear Water Bay Road, Hong Kong, China.
Choi
Roy C Y
RC
Leung
K Wing
KW
Siow
Nina L
NL
Kong
Ling W
LW
Lau
Faye T C
FT
Peng
H Benjamin
HB
Tsim
Karl W K
KW
D000110:Acetylcholinesterase / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000737:chemistry; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D024510:Muscle Development; D009132:Muscles / Q000201:enzymology*; D018008:Myogenin / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism / Q000502:physiology*; D009474:Neurons / Q000378:metabolism; D011392:Proline / Q000737:chemistry*; D012333:RNA, Messenger / Q000378:metabolism*; D012584:Sciatic Nerve / Q000378:metabolism; D014158:Transcription, Genetic
D008565:Membrane Proteins; D018008:Myogenin; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C486718:prima1 protein, mouse; D011392:Proline; D000110:Acetylcholinesterase; D015740:Calcitonin Gene-Related Peptide