PMID- 18362153
OWN - NLM
STAT- MEDLINE
DCOM- 20080718
LR  - 20220309
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 283
IP  - 21
DP  - 2008 May 23
TI  - Sortilin-related receptor with A-type repeats (SORLA) affects the amyloid 
      precursor protein-dependent stimulation of ERK signaling and adult neurogenesis.
PG  - 14826-34
LID - 10.1074/jbc.M710574200 [doi]
AB  - Sortilin-related receptor with A-type repeats (SORLA) is a sorting receptor that 
      impairs processing of amyloid precursor protein (APP) to soluble (s) APP and to 
      the amyloid beta-peptide in cultured neurons and is poorly expressed in patients 
      with Alzheimer disease (AD). Here, we evaluated the consequences of Sorla gene 
      defects on brain anatomy and function using mouse models of receptor deficiency. 
      In line with a protective role for SORLA in APP metabolism, lack of the receptor 
      results in increased amyloidogenic processing of endogenous APP and in aggravated 
      plaque deposition when introduced into PDAPP mice expressing mutant human APP. 
      Surprisingly, increased levels of sAPP caused by receptor deficiency correlate 
      with pro-found stimulation of neuronal ERK signaling and with enhanced 
      neurogenesis, providing in vivo support for neurotrophic functions of sAPP. Our 
      data document a role for SORLA not only in control of plaque burden but also in 
      APP-dependent neuronal signaling and suggest a molecular explanation for 
      increased neurogenesis observed in some AD patients.
FAU - Rohe, Michael
AU  - Rohe M
AD  - Max-Delbrueck-Center for Molecular Medicine, Berlin, Germany.
FAU - Carlo, Anne-Sophie
AU  - Carlo AS
FAU - Breyhan, Henning
AU  - Breyhan H
FAU - Sporbert, Anje
AU  - Sporbert A
FAU - Militz, Daniel
AU  - Militz D
FAU - Schmidt, Vanessa
AU  - Schmidt V
FAU - Wozny, Christian
AU  - Wozny C
FAU - Harmeier, Anja
AU  - Harmeier A
FAU - Erdmann, Bettina
AU  - Erdmann B
FAU - Bales, Kelly R
AU  - Bales KR
FAU - Wolf, Susanne
AU  - Wolf S
FAU - Kempermann, Gerd
AU  - Kempermann G
FAU - Paul, Steven M
AU  - Paul SM
FAU - Schmitz, Dietmar
AU  - Schmitz D
FAU - Bayer, Thomas A
AU  - Bayer TA
FAU - Willnow, Thomas E
AU  - Willnow TE
FAU - Andersen, Olav M
AU  - Andersen OM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080324
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Membrane Transport Proteins)
RN  - 0 (Receptors, LDL)
RN  - 0 (Sorl1 protein, mouse)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
SB  - IM
MH  - Aging/*physiology
MH  - Amyloid beta-Protein Precursor/*metabolism
MH  - Animals
MH  - *Cell Differentiation
MH  - Electrophysiology
MH  - Enzyme Activation
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - *MAP Kinase Signaling System
MH  - Membrane Transport Proteins/deficiency/genetics/*metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Neurons/*cytology/*metabolism
MH  - Patch-Clamp Techniques
MH  - Receptors, LDL/deficiency/genetics/*metabolism
EDAT- 2008/03/26 09:00
MHDA- 2008/07/19 09:00
CRDT- 2008/03/26 09:00
PHST- 2008/03/26 09:00 [pubmed]
PHST- 2008/07/19 09:00 [medline]
PHST- 2008/03/26 09:00 [entrez]
AID - S0021-9258(20)54350-0 [pii]
AID - 10.1074/jbc.M710574200 [doi]
PST - ppublish
SO  - J Biol Chem. 2008 May 23;283(21):14826-34. doi: 10.1074/jbc.M710574200. Epub 2008 
      Mar 24.