title: ApoER2 function in the establishment and maintenance of retinal synaptic connectivity.
abstract: 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.
authors: Molecular Pharmacology and Physiology, USF Health Byrd Alzheimer's Institute, University of South Florida, Tampa, Florida 33613, USA.
authors: Justin H
authors: JH
authors: Trotter
authors: Martin
authors: M
authors: Klein
authors: Umesh K
authors: UK
authors: Jinwal
authors: Jose F
authors: JF
authors: Abisambra
authors: Chad A
authors: CA
authors: Dickey
authors: Jeremy
authors: J
authors: Tharkur
authors: Irene
authors: I
authors: Masiulis
authors: Jindong
authors: J
authors: Ding
authors: Kirsten G
authors: KG
authors: Locke
authors: Catherine Bowes
authors: CB
authors: Rickman
authors: David G
authors: DG
authors: Birch
authors: Edwin J
authors: EJ
authors: Weeber
authors: Joachim
authors: J
authors: Herz
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D005260:Female; D026502:LDL-Receptor Related Proteins / Q000502:physiology*; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008818:Mice, Neurologic Mutants; D009434:Neural Pathways / Q000378:metabolism / Q000502:physiology; D000091042:Reelin Protein; D012160:Retina / Q000254:growth & development* / Q000378:metabolism; D017948:Retinal Rod Photoreceptor Cells / Q000378:metabolism / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D026502:LDL-Receptor Related Proteins; D000091042:Reelin Protein; C098773:low density lipoprotein receptor-related protein 8; C000717128:Reln protein, mouse