Activity-dependent expression of acyl-coenzyme a-binding protein in retinal muller glial cells evoked by optokinetic stimulation.
Long-term horizontal optokinetic stimulation (HOKS) decreases the gain of the horizontal optokinetic reflex and evokes the second phase of optokinetic afternystagmus (OKAN-II). We investigated the possible molecular constituents of this adaptation. We used a differential display reverse transcriptase-PCR screen for mRNAs isolated from retinas of rabbits that received HOKS. In each rabbit, we compared mRNAs from the retina stimulated in the posterior-->anterior (preferred) direction with mRNAs from the retina stimulated in the anterior-->posterior (null) direction. Acyl-CoA-binding protein (ACBP) mRNA was one of four mRNAs selected by this screen, the proteins of which interact with GABA receptors. HOKS in the preferred direction increased ACBP mRNA transcription and ACBP protein expression. ACBP was localized to Muller glial cells by hybridization histochemistry and by immunohistochemistry. ACBP interacts with the alpha1-subunit of the GABA(A) receptor, as determined by a yeast two-hybrid technique. This interaction was confirmed by coimmunoprecipitation of ACBP and the alpha1-subunit of the GABA(A) receptor using an antibody to GABA(A)alpha1. The interaction was also confirmed by a "pull-down" assay in which histidine-tagged ACBP was used to pull down the GABA(A)alpha1. ACBP does not cross the blood-brain barrier. However, smaller truncated proteolytic fragments of ACBP do, increasing the excitability of central cortical neurons. Muller cells may secrete ACBP in the inner plexiform layer, thereby decreasing the sensitivity of GABA(A) receptors expressed on the surface of ganglion cell dendrites. Because retinal directional sensitivity is linked to GABAergic transmission, HOKS-induced expression of ACBP could provide a molecular basis for adaptation to HOKS and for the genesis of OKAN-II.
Barmack
Neal H
NH
Neurological Sciences Institute, Oregon Health and Science University, Beaverton, Oregon 97006, USA. barmackn@ohsu.edu
Bilderback
Timothy R
TR
Liu
Henry
H
Qian
Zuyuan
Z
Yakhnitsa
Vadim
V
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001923:Brain Chemistry; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D026261:Diazepam Binding Inhibitor / Q000378:metabolism*; D020869:Gene Expression Profiling; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D009457:Neuroglia / Q000378:metabolism*; D017120:Nystagmus, Optokinetic / Q000502:physiology*; D010775:Photic Stimulation / Q000379:methods; D010812:Physical Stimulation / Q000379:methods; D021122:Protein Subunits / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D011963:Receptors, GABA-A / Q000378:metabolism; D012160:Retina / Q000378:metabolism / Q000502:physiology*; D020798:Two-Hybrid System Techniques
D002352:Carrier Proteins; D026261:Diazepam Binding Inhibitor; D021122:Protein Subunits; D012333:RNA, Messenger; D011963:Receptors, GABA-A