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Polysialic acid limits choline acetyltransferase activity induced by brain‐derived neurotrophic factor
Author(s) -
Burgess Alison,
Aubert Isabelle
Publication year - 2006
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2006.04110.x
Subject(s) - choline acetyltransferase , tropomyosin receptor kinase b , polysialic acid , brain derived neurotrophic factor , trk receptor , neurotrophic factors , medicine , chemistry , endocrinology , neurotrophin , nerve growth factor , receptor , cholinergic , microbiology and biotechnology , neuroscience , biology , biochemistry , neural cell adhesion molecule , cell adhesion , cell
Choline acetyltransferase (ChAT), the enzyme synthesizing acetylcholine, is known to be activated by brain derived neurotrophic factor (BDNF). We found that the specific removal of the carbohydrate polysialic acid (PSA) significantly increased BDNF‐induced ChAT‐activity in embryonic septal neurons. Using a p75 neurotrophin receptor (p75 NTR ) function‐blocking antibody and K252a, a‐pan tropomyosin related kinase (Trk) inhibitor, we demonstrate that BDNF‐induced ChAT activity requires the stimulation of p75 NTR and TrkB. PSA removal drastically increased radioactive iodinated ([ 125 I])BDNF's maximal binding capacity (Bmax), derived from concentrations of [ 125 I]BDNF ranging from 1 pM to 3.2 nM. In the presence of unlabeled nerve growth factor to prevent the binding of [ 125 I]BDNF to p75 NTR sites, the impact of PSA removal on the binding capacity of [ 125 I]BDNF was greatly reduced. In conclusion, PSA limits BDNF‐induced ChAT activity and BDNF–receptor interactions. BDNF‐induced ChAT activity is TrkB and p75 NTR dependent, and upon PSA removal the additional binding of BDNF to its receptors, especially p75 NTR , likely contributes to the maximal ChAT activity observed. In vivo , the ontogenetic loss of PSA in the postnatal period may allow more interactions between BDNF and its receptors to increase ChAT activity and assure the proper development of the cholinergic septal neurons.