PMID- 7876092
OWN - NLM
STAT- MEDLINE
DCOM- 19950331
LR  - 20210318
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 270
IP  - 8
DP  - 1995 Feb 24
TI  - Characterization of sorting signals in the beta-amyloid precursor protein 
      cytoplasmic domain.
PG  - 3565-73
AB  - The beta-amyloid precursor protein (APP) is proteolytically processed to generate 
      beta-amyloid protein, the principal protein component of neuropathological 
      lesions characteristic of Alzheimer's disease. To investigate potential sorting 
      signals in the cytoplasmic tail of APP, we transplanted APP cytoplasmic tail 
      sequences into the cytoplasmic tail of the human transferrin receptor (TR) and 
      showed that two sequence motifs from the APP cytoplasmic tail promote TR 
      internalization. One sequence, GYENPTY, is related to the low density lipoprotein 
      receptor internalization signal, FDNPVY, but also involves a critical glycine 
      residue; the other, YTSI, conforms to the 4-residue tyrosine-based 
      internalization signal consensus sequence. Furthermore, a chimeric molecule 
      (APP-TR) consisting of the cytoplasmic domain of APP and the transmembrane and 
      external domains of TR was rapidly internalized enabling the transport of iron 
      into the cell at approximately 50% the rate of wild-type TR. Alanine scanning 
      mutations indicated that the two sequences identified in transplantation 
      experiments were required for internalization of the chimera. Metabolic 
      pulse-chase experiments showed that the APP-TR chimeras were degraded in a 
      post-Golgi membrane compartment within 2-4 h following normal glycosylation. 
      Degradation was partially dependent upon the two internalization signals and was 
      inhibited by ammonium chloride. A fraction of APP-TR chimeras traffic to a 
      degradative endocytic compartment after appearing on the cell surface. Comparison 
      of soluble APP released from cells expressing either full-length human APP or 
      mutant APP with the sequence YENPTY deleted indicated that this sequence is 
      required for sorting of full-length APP along similar trafficking pathways as the 
      APP-TR chimera.
FAU - Lai, A
AU  - Lai A
AD  - Department of Cancer Biology, Salk Institute, San Diego, California 92186-5800.
FAU - Sisodia, S S
AU  - Sisodia SS
FAU - Trowbridge, I S
AU  - Trowbridge IS
LA  - eng
GR  - GM07198/GM/NIGMS NIH HHS/United States
GR  - NS20471/NS/NINDS NIH HHS/United States
GR  - NSAG05146/NS/NINDS NIH HHS/United States
GR  - etc.
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (DNA Primers)
RN  - 0 (Protein Sorting Signals)
RN  - 0 (Receptors, Transferrin)
RN  - 0 (Recombinant Fusion Proteins)
SB  - IM
MH  - Amino Acid Sequence
MH  - Amyloid beta-Protein Precursor/*metabolism
MH  - Animals
MH  - Base Sequence
MH  - CHO Cells
MH  - Cell Compartmentation
MH  - Cricetinae
MH  - Cytoplasm/metabolism
MH  - DNA Primers
MH  - Endocytosis
MH  - Golgi Apparatus/metabolism
MH  - Humans
MH  - Molecular Sequence Data
MH  - Protein Sorting Signals/*metabolism
MH  - Receptors, Transferrin/metabolism
MH  - Recombinant Fusion Proteins/metabolism
EDAT- 1995/02/24 00:00
MHDA- 1995/02/24 00:01
CRDT- 1995/02/24 00:00
PHST- 1995/02/24 00:00 [pubmed]
PHST- 1995/02/24 00:01 [medline]
PHST- 1995/02/24 00:00 [entrez]
AID - S0021-9258(18)94829-5 [pii]
PST - ppublish
SO  - J Biol Chem. 1995 Feb 24;270(8):3565-73.