ApoER2 function in the establishment and maintenance of retinal synaptic connectivity

Justin H. Trotter, Martin Klein, Umesh K. Jinwal, Jose F. Abisambra, Chad A. Dickey, Jeremy Tharkur, Irene Masiulis, Jindong Ding, Kirsten G. Locke, Catherine Bowes Rickman, David G. Birch, Edwin J. Weeber, Joachim Herz

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

The cellular and molecular mechanisms responsible for the development of inner retinal circuitry are poorly understood. Reelin and apolipoproteinE (apoE), ligands of apoE receptor 2 (ApoER2), are involved in retinal development and degeneration, respectively. Here we describe the function of ApoER2 in the developing and adult retina. ApoER2 expression was highest during postnatal inner retinal synaptic development and was consider a blylower in the mature retina. Both during development and in the adult, ApoER2 was expressed by A-II amacrine cells. ApoER2 knock-out (KO) mice had rod bipolar morphogenic defects, altered A-II a macrinedendritic development, and impaired rod-driven retinal responses. The presence of an intact ApoER2 NPxY motif, necessary for binding Disabled-1 and transducing the Reelin signal, was also necessary for development of the rod bipolar pathway, while the alternatively spliced exon 19 was not. Mice deficient in another Reelin receptor, very low-density lipoprotein receptor (VLDLR), had normal rod bipolar morphology but altered A-II amacrine dendritic development. VLDLR KO mice also had reductions in oscillatory potentials and delayed synaptic response intervals. Interestingly, age-related reductions in rod and cone function were observed in both ApoER2 and VLDLR KOs. These results support a pivotal role for ApoER2 in the establishment and maintenance of normal retinal synaptic connectivity.

Original languageEnglish (US)
Pages (from-to)14413-14423
Number of pages11
JournalJournal of Neuroscience
Volume31
Issue number40
DOIs
StatePublished - Oct 5 2011

ASJC Scopus subject areas

  • Neuroscience(all)

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    Trotter, J. H., Klein, M., Jinwal, U. K., Abisambra, J. F., Dickey, C. A., Tharkur, J., Masiulis, I., Ding, J., Locke, K. G., Rickman, C. B., Birch, D. G., Weeber, E. J., & Herz, J. (2011). ApoER2 function in the establishment and maintenance of retinal synaptic connectivity. Journal of Neuroscience, 31(40), 14413-14423. https://doi.org/10.1523/JNEUROSCI.3135-11.2011