title: Fyn tyrosine kinase increases Apolipoprotein E Receptor 2 levels and phosphorylation.
abstract: Apolipoprotein E Receptor 2 (ApoER2) and the tyrosine kinase Fyn are both members of the Reelin pathway, a signaling pathway essential for the laminar formation of the cortex during development and proper dendritic spine density and long-term potential (LTP) in the adult brain. In the presence of extracellular Reelin, ApoER2 binds the intracellular protein Dab1, an adaptor protein that is phosphorylated by Fyn. However, direct interactions between ApoER2 and Fyn are not well defined. Here, we show that total levels of ApoER2 and surface levels of ApoER2 are increased by active Fyn. Via a separate mechanism, ApoER2 is also phosphorylated by Fyn, an event that peaks in the postnatal cortex at day 5 and can occur at multiple ApoER2 tyrosine residues. Dab1 is also involved in this phosphorylation, promoting the phosphorylation of ApoER2 by Fyn when it is itself phosphorylated. These results elucidate some of the intracellular mechanisms that give rise to a functional Reelin pathway.
authors.affiliation: Department of Neuroscience, Georgetown University Medical Center, Washington, District of Columbia, United States of America.
authors.forename: Teal C
authors.initials: TC
authors.lastname: Burrell
authors.affiliation: Department of Neuroscience, Georgetown University Medical Center, Washington, District of Columbia, United States of America.
authors.forename: Shailaja D
authors.initials: SD
authors.lastname: Divekar
authors.affiliation: Department of Molecular Pharmacology and Physiology, University of South Florida Health Byrd Alzheimer's Institute, University of South Florida, Tampa, Florida, United States of America.
authors.forename: Edwin J
authors.initials: EJ
authors.lastname: Weeber
authors.affiliation: Department of Neuroscience, Georgetown University Medical Center, Washington, District of Columbia, United States of America.
authors.forename: G William
authors.initials: GW
authors.lastname: Rebeck
mesh_terms: D000818:Animals; D019921:Biotinylation; D001921:Brain / Q000378:metabolism; D019556:COS Cells; D002522:Chlorocebus aethiops; D005786:Gene Expression Regulation; D026502:LDL-Receptor Related Proteins / Q000378:metabolism*; D017774:Long-Term Potentiation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D051076:Proto-Oncogene Proteins c-fyn / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000091042:Reelin Protein; D015398:Signal Transduction
chemical_list: D026502:LDL-Receptor Related Proteins; D000091042:Reelin Protein; C000717129:Reln protein, rat; C098773:low density lipoprotein receptor-related protein 8; C494960:Fyn protein, mouse; C494961:Fyn protein, rat; D051076:Proto-Oncogene Proteins c-fyn; C000717128:Reln protein, mouse