Expression and subcellular localization of a novel nuclear acetylcholinesterase protein.
Acetylcholine is found in the nervous system and also in other cell types (endothelium, lymphocytes, and epithelial and blood cells), which are globally termed the non-neuronal cholinergic system. In this study we investigated the expression and subcellular localization of acetylcholinesterase (AChE) in endothelial cells. Our results show the expression of the 70-kDa AChE in both cytoplasmic and nuclear compartments. We also describe, for the first time, a nuclear and cytoskeleton-bound AChE isoform with approximately 55 kDa detected in endothelial cells. This novel isoform is decreased in response to vascular endothelial growth factor via the proteosomes pathway, and it is down-regulated in human leukemic T-cells as compared with normal T-cells, suggesting that the decreased expression of the 55-kDa AChE protein may contribute to an angiogenic response and associate with tumorigenesis. Importantly, we show that its nuclear expression is not endothelial cell-specific but also evidenced in non-neuronal and neuronal cells. Concerning neuronal cells, we can distinguish an exclusively nuclear expression in postnatal neurons in contrast to a cytoplasmic and nuclear expression in embryonic neurons, suggesting that the cell compartmentalization of this new AChE isoform is changed during the development of nervous system. Overall, our studies suggest that the 55-kDa AChE may be involved in different biological processes such as neural development, tumor progression, and angiogenesis.
Santos
Susana Constantino Rosa
SC
Instituto de Biopatologia Química, Faculdade de Medicina de Lisboa, 1649-028 Lisboa, Portugal. sconstantino@fm.ul.pt
Vala
Inês
I
Miguel
Cláudia
C
Barata
João T
JT
Garção
Pedro
P
Agostinho
Paula
P
Mendes
Marta
M
Coelho
Ana V
AV
Calado
Angelo
A
Oliveira
Catarina R
CR
e Silva
João Martins
JM
Saldanha
Carlota
C
D000109:Acetylcholine / Q000378:metabolism; D000110:Acetylcholinesterase / Q000096:biosynthesis*; D000818:Animals; D002467:Cell Nucleus / Q000201:enzymology*; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D002490:Central Nervous System / Q000196:embryology / Q000201:enzymology; D003599:Cytoskeleton / Q000201:enzymology*; D042783:Endothelial Cells / Q000201:enzymology*; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D019169:Jurkat Cells; D020014:K562 Cells; D007938:Leukemia / Q000201:enzymology; D009389:Neovascularization, Pathologic / Q000201:enzymology*; D009928:Organ Specificity; D016716:PC12 Cells; D020033:Protein Isoforms / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar
D020033:Protein Isoforms; D000110:Acetylcholinesterase; D000109:Acetylcholine