Most acetylcholinesterase activity of non-nervous tissues and cells arises from the AChE-H transcript.
While the functional implications of AChE-T, PRiMA and ColQ have been firmly established, those of glypiated AChE remain uncertain. Insights into the physiological meaning of glycosylphosphatidylinositol (GPI)-linked AChE-H were gained by comparing nervous and non-nervous tissues for the amount of AChE mRNA variants they contained. PCR showed that AChE-T mRNA prevailed in the mouse brain, spinal cord, sciatic nerve and muscle, and AChE-H mRNA in the bone marrow and thymus, as well as in the human gut. The similar levels of AChE-T and AChE-H mRNAs in mouse liver and human kidney contrasted with the almost exclusive presence of catalytically active AChE-H in both organs. The absence of PRiMA mRNA in liver suggested that the tetramers made of AChE-T fail to bind to the cell membrane and are secreted due to the lack of PRiMA in non-nervous organs. In contrast, glypiated AChE-H is largely and lastingly bound to the cell membrane. Thus, non-synaptic glypiated AChE-H seems to be the counterpart of synaptic PRiMA-linked AChE-T, the former designed for clearing ACh waves, the latter for confronting ACh bursts, and both for helping to protect cells against the harmful effects of durable nicotinic and muscarinic activation.
Departamento de Bioquímica y Biología Molecular-A, Universidad de Murcia, Regional Campus of International Excellence "Campus Mare Nostrum", Murcia, Spain.
María Fernanda
MF
Montenegro
Susana
S
Nieto-Cerón
Juan
J
Cabezas-Herrera
Encarnación
E
Muñoz-Delgado
Francisco Javier
FJ
Campoy
Cecilio J
CJ
Vidal
D000110:Acetylcholinesterase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000201:enzymology; D017261:Glycosylphosphatidylinositols / Q000378:metabolism; D006801:Humans; D007422:Intestines / Q000201:enzymology; D007668:Kidney / Q000201:enzymology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009132:Muscles / Q000201:enzymology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009928:Organ Specificity; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D013116:Spinal Cord / Q000201:enzymology
D017261:Glycosylphosphatidylinositols; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C486718:prima1 protein, mouse; D000110:Acetylcholinesterase