title: FE65 as a link between VLDLR and APP to regulate their trafficking and processing.
abstract: BACKGROUND
  Several studies found that FE65, a cytoplasmic adaptor protein, interacts with APP and LRP1, altering the trafficking and processing of APP. We have previously shown that FE65 interacts with the ApoE receptor, ApoER2, altering its trafficking and processing. Interestingly, it has been shown that FE65 can act as a linker between APP and LRP1 or ApoER2. In the present study, we tested whether FE65 can interact with another ApoE receptor, VLDLR, thereby altering its trafficking and processing, and whether FE65 can serve as a linker between APP and VLDLR.
  
  
  RESULTS
  We found that FE65 interacted with VLDLR using GST pull-down and co-immunoprecipitation assays in COS7 cells and in brain lysates. This interaction occurs via the PTB1 domain of FE65. Co-transfection with FE65 and full length VLDLR increased secreted VLDLR (sVLDLR); however, the levels of VLDLR C-terminal fragment (CTF) were undetectable as a result of proteasomal degradation. Additionally, FE65 increased cell surface levels of VLDLR. Moreover, we identified a novel complex between VLDLR and APP, which altered trafficking and processing of both proteins. Furthermore, immunoprecipitation results demonstrated that the presence of FE65 increased the interaction between APP and VLDLR in vitro and in vivo.
  
  
  CONCLUSIONS
  These data suggest that FE65 can regulate VLDLR trafficking and processing. Additionally, the interaction between VLDLR and APP altered both protein's trafficking and processing. Finally, our data suggest that FE65 serves as a link between VLDLR and APP. This novel interaction adds to a growing body of literature indicating trimeric complexes with various ApoE Receptors and APP.
authors.affiliation: Department of Neuroscience, Georgetown University Medical Center, 3970 Reservoir Road NW, Washington, DC 20057-1464, USA.
authors.forename: Sonya B
authors.initials: SB
authors.lastname: Dumanis
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Chamberlain
authors.forename: Yoo
authors.initials: Y
authors.lastname: Jin Sohn
authors.forename: Young
authors.initials: Y
authors.lastname: Jin Lee
authors.forename: Suzanne Y
authors.initials: SY
authors.lastname: Guénette
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Suzuki
authors.forename: Paul M
authors.initials: PM
authors.lastname: Mathews
authors.forename: Daniel Ts
authors.initials: DTs
authors.lastname: Pak
authors.forename: G William
authors.initials: GW
authors.lastname: Rebeck
authors.forename: Yoo-Hun
authors.initials: YH
authors.lastname: Suh
authors.forename: Hee-Sae
authors.initials: HS
authors.lastname: Park
authors.forename: Hyang-Sook
authors.initials: HS
authors.lastname: Hoe
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D019556:COS Cells; D002522:Chlorocebus aethiops; D047468:Immunoprecipitation; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011973:Receptors, LDL / Q000378:metabolism*; D014162:Transfection
chemical_list: D016564:Amyloid beta-Protein Precursor; C486242:Apbb1 protein, rat; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D011973:Receptors, LDL; C036053:VLDL receptor