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

Zuyuan Qian, Timothy R. Bilderback, Neal H. Barmack

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Horizontal 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 Müller cells. If the expressed ACBP were also secreted by Müller 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 Müller glial cells and Müller-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 GABA A receptors than did unphosphorylated ODN or unphosphorylated ACBP. We conclude that stimulus-induced Müller cell secretion of phosphorylated ACBP could influence the GABAergic transmission in neighboring retinal neurons.

Original languageEnglish (US)
Pages (from-to)1287-1299
Number of pages13
JournalJournal of Neurochemistry
Volume105
Issue number4
DOIs
StatePublished - May 1 2008

Keywords

  • Acyl coenzyme A-binding protein secretion
  • Astrocytes
  • Direction selectivity
  • Glial cells
  • Müller
  • QNR/K2 cells
  • Retina
  • Threonine phosphorylation

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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