ApoER2 function in the establishment and maintenance of retinal synaptic connectivity.

Published

Journal Article

The cellular and molecular mechanisms responsible for the development of inner retinal circuitry are poorly understood. Reelin and apolipoprotein E (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 considerably lower 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 amacrine dendritic 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.

Full Text

Duke Authors

Cited Authors

  • Trotter, JH; Klein, M; Jinwal, UK; Abisambra, JF; Dickey, CA; Tharkur, J; Masiulis, I; Ding, J; Locke, KG; Rickman, CB; Birch, DG; Weeber, EJ; Herz, J

Published Date

  • October 2011

Published In

Volume / Issue

  • 31 / 40

Start / End Page

  • 14413 - 14423

PubMed ID

  • 21976526

Pubmed Central ID

  • 21976526

Electronic International Standard Serial Number (EISSN)

  • 1529-2401

International Standard Serial Number (ISSN)

  • 0270-6474

Digital Object Identifier (DOI)

  • 10.1523/JNEUROSCI.3135-11.2011

Language

  • eng