HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: iovs.08-2758v1 50/2/505    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Specht, D. Articles by tom Dieck, S. Search for Related Content PubMed PubMed Citation Articles by Specht, D. Articles by tom Dieck, S.

Effects of Presynaptic Mutations on a Postsynaptic Cacna1s Calcium Channel Colocalized with mGluR6 at Mouse Photoreceptor Ribbon Synapses

¹From the Department of Biology, Animal Physiology, University of Erlangen-Nuremberg, Erlangen, Germany; the ²Department of Neuroanatomy, Max Planck Institute for Brain Research, Frankfurt/Main, Germany; the ³Department of Biochemistry, University of Otago, Dunedin, New Zealand; ⁴Ozgene Pty. LtD, Bentley, Western Australia, Australia; and the ⁵Department of Cell and Matrix Biology, Institute of Zoology, Johannes Gutenberg University of Mainz, Mainz, Germany

PURPOSE. Photoreceptor ribbon synapses translate light-dependent changes of membrane potential into graded transmitter release via L-type voltage-dependent calcium channel (VDCC) activity. Functional abnormalities (e.g., a reduced electroretinogram b-wave), arising from mutations of presynaptic proteins, such as Bassoon and the VDCC1 subunit Cacna1f, have been shown to altered transmitter release. L-type VDCC1 subtype expression in wild-type and mutant mice was examined, to investigate the underlying pathologic mechanism.

METHODS. Two antisera against Cacna1f, and a Cacna1f mouse mutant (Cacna1fEx14-17) were generated. Immunocytochemistry for L-type VDCC1 subunits and additional synaptic marker proteins was performed in wild-type, BassoonEx4-5 and Cacna1fEx14-17 mice.

RESULTS. Active zone staining at photoreceptor ribbon synapses with a pan1 antibody colocalized with staining for Cacna1f in wild-type mouse retina. Similarly, in the BassoonEx4-5 mouse, residual mislocalized staining for pan1 and Cacna1f showed colocalization. Unlike the presynaptic location of Cacna1f and pan1 antibody staining, the skeletal muscle VDCC1 subunit Cacna1s was present postsynaptically at ON-bipolar cell dendrites, where it colocalized with metabotropic glutamate receptor 6 (mGluR6). Surprisingly, Cacna1s labeling was severely downregulated in the BassoonEx4-5 and Cacna1fEx14-17 mutants. Subsequent analyses revealed severely reduced ON-bipolar cell dendritic expression of the sarcoplasmic reticulum Ca²⁺ ATPase Serca2 in both mouse mutants and of mGluR6 in the Cacna1fEx14-17 mutant.

CONCLUSIONS. Presynaptic mutations leading to reduced photoreceptor-to-bipolar cell signaling are associated with disturbances in protein expression within postsynaptic dendrites. Moreover, detection of Cacna1s and Serca2 in ON-bipolar cell dendrites in wild-type animals suggests a putative role in regulation of postsynaptic Ca²⁺ flux.