title: EPAC-STX interaction may play a role in neurodevelopment/neurogenesis.
abstract: During embryonic life a group of cells become proliferated, migrated and differentiated to develop central nervous system. Migration has been suggested to be due to accumulation of polysialic acid (PSA), a negatively-charged glycoside, on the outer cell membrane. The same event happens to PSA in a tumor mass as well. Polysialylation is the product of polysialyl transfrase isozymes; STX (ST8SIA2), the embryonic active isoform, and PST (ST8SIA4), expressed in adults CNS. Additionally, cAMP concludes to activation of PKA and EPAC resulting to the initiation of gene expressions which are highly required during development. EPAC, the latter known target of cAMP in mammalian nervous system, has proliferative properties in the developing CNS. We propose for the proper action of EPAC, namely CNS development, the presence of STX and its elevation after EPAC activation is mandatory. This hypothesis is put forward after observing, in a preliminary experiment, a relationship between EPAC activation and STX mRNA expression levels in rat hippocampus. The interaction between EPAC and STX may be suggested to be through EPAC-induced gene expression of the latter. From the above assumptions one may suggest the use of EPAC activators as neurogenesis inducers and its inhibitors as tumor modulators.
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. arazmi@razi.tums.ac.ir
authors.forename: Ali
authors.initials: A
authors.lastname: Razmi
authors.forename: Samane
authors.initials: S
authors.lastname: Jahanabadi
authors.forename: Mousa
authors.initials: M
authors.lastname: Sahebgharani
authors.forename: Mohammad-Reza
authors.initials: MR
authors.lastname: Zarrindast
mesh_terms: D020662:Guanine Nucleotide Exchange Factors / Q000502:physiology*; D006801:Humans; D008962:Models, Theoretical; D055495:Neurogenesis; D022621:Shiga Toxin / Q000378:metabolism*
chemical_list: D020662:Guanine Nucleotide Exchange Factors; C116122:RAPGEF3 protein, human; D022621:Shiga Toxin