title: Effects of PS1 deficiency on membrane protein trafficking in neurons.
abstract: We have examined the trafficking and metabolism of the beta-amyloid precursor protein (APP), an APP homolog (APLP1), and TrkB in neurons that lack PS1. We report that PS1-deficient neurons fail to secrete Abeta, and that the rate of appearance of soluble APP derivatives in the conditioned medium is increased. Remarkably, carboxyl-terminal fragments (CTFs) derived from APP and APLP1 accumulate in PS1-deficient neurons. Hence, PS1 plays a role in promoting intramembrane cleavage and/or degradation of membrane-bound CTFs. Moreover, the maturation of TrkB and BDNF-inducible TrkB autophosphorylation is severely compromised in neurons lacking PS1. We conclude that PS1 plays an essential role in modulating trafficking and metabolism of a selected set of membrane and secretory proteins in neurons.
authors.affiliation: Department of Pharmacological and Physiological Sciences, The University of Chicago, Illinois 60637, USA.
authors.forename: S
authors.initials: S
authors.lastname: Naruse
authors.forename: G
authors.initials: G
authors.lastname: Thinakaran
authors.forename: J J
authors.initials: JJ
authors.lastname: Luo
authors.forename: J W
authors.initials: JW
authors.lastname: Kusiak
authors.forename: T
authors.initials: T
authors.lastname: Tomita
authors.forename: T
authors.initials: T
authors.lastname: Iwatsubo
authors.forename: X
authors.initials: X
authors.lastname: Qian
authors.forename: D D
authors.initials: DD
authors.lastname: Ginty
authors.forename: D L
authors.initials: DL
authors.lastname: Price
authors.forename: D R
authors.initials: DR
authors.lastname: Borchelt
authors.forename: P C
authors.initials: PC
authors.lastname: Wong
authors.forename: S S
authors.initials: SS
authors.lastname: Sisodia
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D005333:Fetus; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D053764:Presenilin-1
chemical_list: D016564:Amyloid beta-Protein Precursor; D008565:Membrane Proteins; D053764:Presenilin-1