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Chapter 5,828

Long duration phosphorylation of synaptic membrane proteins

Ng, M.; Matus, A.

Neuroscience 4(9): 1265-1274

1979


ISSN/ISBN: 0306-4522
PMID: 492536
DOI: 10.1016/0306-4522(79)90156-8
Accession: 005827163

It was proposed that the phosphorylation of membrane proteins is the mechanism by which postsynaptic membrane permeability is controlled at catecholaminergic synapses. Part of the evidence in favor of this interpretation is the rapid turnover of protein-bound phosphate observed in isolated synaptosomal plasma membranes in vitro. The rate of incorporation of phosphate from [.gamma.-32P]ATP into the protein of synaptic membranes isolated from rat brain was dependent upon the concentration of ATP. At 10 .mu.M, maximum phosphate incorporation occurred after 30 s but at 1 .mu.M the maximum was not reached until 5 min. The net amount of phosphate incorporated also rose with increasing ATP concentration, being lowest at 10 .mu.M and rising to reach a maximum at between 1 and 5 mM. When the phosphorylation of individual synaptic membrane proteins was followed by gel electrophoresis and autoradiography even more pronounced differences were found between the 2 concentrations of ATP: at 10 .mu.M there was a rapid phosphorylation and a striking stimulation by cyclic(c)AMP whereas at 1 mM the time-course of turnover was prolonged and stimulation by cAMP was more modest. At both concentrations of ATP the phosphorylation of synaptic membrane proteins was not completely reversible in vitro. In both cases > 50% of the incorporated phosphate was still bound to membrane protein after dephosphorylation had ceased. Results obtained with micromolar concentrations of ATP are probably spurious, the phosphorylation process being prematurely terminated by the consumption of the substrate by non-kinase membrane ATPase activity. The longer time-course found with adequate levels of ATP (mmolar concentrations) is not incompatible with a transmission-dependent role for synaptic membrane phosphorylation. The phenomenon may be part of a more general metabolic response to afferent stimulation than has hitherto been proposed.

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