Acyl coenzyme A-binding protein (ACBP) is phosphorylated and secreted by retinal Mueller astrocytes following protein kinase C activation

• Published in: Journal of neurochemistry Vol. 105; no. 4; pp. 1287 - 1299
• Main Authors: Qian, Zuyuan, Bilderback, Timothy R, Barmack, Neal H
• Format: Journal Article
• Language: English
• Published: 01.05.2008
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2008.05229.x

AbstractHorizontal optokinetic stimulation of rabbit retina in vivo evokes increased expression of acyl coenzyme A-binding protein (ACBP), also known as 'diazepam binding inhibitor,' from retinal Mueller cells. If the expressed ACBP were also secreted by Mueller cells, then stimulus-evoked secretion of ACBP could influence the activity of GABAA receptor-expressing retinal neurons. In this study, we examine in vitro whether ACBP is secreted by Mueller glial cells and Mueller-like QNR/K2 cells following stimulation with elevated levels of KCl and phorbol myristic acetate (PMA). KCl and PMA stimulation evoked secretion of threonine-phosphorylated ACBP. A sequence analysis of ACBP shows that it has five potential phosphorylation sites: Two threonine sites fit a protein kinase C phosphorylation pattern. Two threonine sites fit a casein kinase II (CK2) pattern. One serine site fits a CK2 pattern. As CK2 is not expressed in QNR/K2 cells, it is probable that protein kinase C accounts for the phosphorylation of ACBP in these cells and for the PMA-evoked secretion of ACBP. Serine phosphorylation was constitutive. Horizontal optokinetic stimulation increased threonine-phosphorylated ACBP in rabbit retina. Phosphorylation of ACBP may influence its target affinity. We used a proteolytic fragment of ACBP, octadecaneuropeptide (ODN), to investigate how threonine phosphorylation influences its affinity for GABAA receptors. Threonine-phosphorylated ODN had a stronger affinity for GABAA receptors than did unphosphorylated ODN or unphosphorylated ACBP. We conclude that stimulus-induced Mueller cell secretion of phosphorylated ACBP could influence the GABAergic transmission in neighboring retinal neurons.