Transcriptional regulation of proline-rich membrane anchor (PRiMA) of globular form acetylcholinesterase in neuron: an inductive effect of neuron differentiation.
The transcriptional regulation of proline-rich membrane anchor (PRiMA), an anchoring protein of tetrameric globular form of acetylcholinesterase (G(4) AChE), was revealed in cultured cortical neurons during differentiation. The level of AChE(T) protein, total enzymatic activity and the amount of G(4) AChE were dramatically increased during the neuron differentiation. RT-PCR analyses revealed that the transcript encoding PRiMA was significantly up-regulated in the differentiated neurons. To investigate the transcriptional mechanism on PRiMA regulation, a reporter construct of human PRiMA promoter-tagged luciferase was employed in this study. Upon the neuronal differentiation in cortical neurons, a mitogen-activated protein (MAP) kinase-dependent pathway was stimulated: this signaling cascade was shown to regulate the transcriptional activity of PRiMA. In addition, both PRiMA and AChE(T) transcripts were induced by the over expression of an active mutant of Raf in the cultured neurons. The treatment of a MAP kinase inhibitor (U0126) significantly blocked the expression of PRiMA transcript and promoter-driven luciferase activity as induced by the differentiation of cortical neurons. These results suggested that a MAP kinase signaling pathway served as one of the transcriptional regulators in controlling PRiMA gene expression during the neuronal differentiation process.
Department of Biology and Center for Chinese Medicine, The Hong Kong University of Science and Technology, Kowloon, Hong Kong SAR, China.
Heidi Q
HQ
Xie
Roy C Y
RC
Choi
K Wing
KW
Leung
Vicky P
VP
Chen
Glanice K Y
GK
Chu
Karl W K
KW
Tsim
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D002460:Cell Line; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009570:Nitriles / Q000494:pharmacology; D010446:Peptide Fragments / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D048490:raf Kinases / Q000235:genetics / Q000378:metabolism
C488971:AchE peptide; D002070:Butadienes; D004791:Enzyme Inhibitors; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D009570:Nitriles; C446290:PRIMA1 protein, human; C508016:PRiMA1 protein, rat; D010446:Peptide Fragments; C113580:U 0126; D048490:raf Kinases; D000110:Acetylcholinesterase