PMID- 11781576
OWN - NLM
STAT- MEDLINE
DCOM- 20020208
LR  - 20190613
IS  - 1465-7392 (Print)
IS  - 1465-7392 (Linking)
VI  - 3
IP  - 12
DP  - 2001 Dec
TI  - Nicastrin is required for Presenilin-mediated transmembrane cleavage in 
      Drosophila.
PG  - 1129-32
AB  - The transmembrane glycoprotein Nicastrin was identified in a complex with the 
      multipass membrane protein Presenilin. Presenilin mediates transmembrane cleavage 
      of single-pass transmembrane proteins with short extracellular domains, including 
      the ligand-activated form of the receptor Notch and beta-amyloid precursor 
      protein (beta-APP). Transmembrane cleavage of Notch is essential for signal 
      transduction, and transmembrane cleavage of beta-APP generates pathogenic amyloid 
      peptides implicated in Alzheimer's disease. Here, we investigate the requirement 
      for Nicastrin in Presenilin-mediated transmembrane cleavage. We show that, in 
      Drosophila, loss of Nicastrin activity blocks the accumulation of Presenilin 
      associated with the apical plasma membrane, abolishes Presenilin-dependent 
      cleavage of the transmembrane domains of Notch and beta-APP, and abrogates Notch 
      signal transduction.
FAU - Chung, H M
AU  - Chung HM
AD  - Department of Genetics and Development, Howard Hughes Medical Institute, Columbia 
      University, College of Physicians and Surgeons, New York, NY 10032, USA.
FAU - Struhl, G
AU  - Struhl G
LA  - eng
PT  - Journal Article
PL  - England
TA  - Nat Cell Biol
JT  - Nature cell biology
JID - 100890575
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Drosophila Proteins)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (N protein, Drosophila)
RN  - 0 (Presenilin-1)
RN  - 0 (Receptors, Notch)
RN  - 0 (nicastrin protein)
RN  - EC 3.4.- (Amyloid Precursor Protein Secretases)
SB  - IM
MH  - Amyloid Precursor Protein Secretases
MH  - Amyloid beta-Protein Precursor/metabolism
MH  - Animals
MH  - Cell Membrane/metabolism
MH  - Drosophila
MH  - Drosophila Proteins
MH  - Membrane Glycoproteins/genetics/*metabolism
MH  - Membrane Proteins/*metabolism
MH  - Mutation/physiology
MH  - Presenilin-1
MH  - Receptors, Notch
MH  - Signal Transduction/physiology
EDAT- 2002/01/10 10:00
MHDA- 2002/02/09 10:01
CRDT- 2002/01/10 10:00
PHST- 2002/01/10 10:00 [pubmed]
PHST- 2002/02/09 10:01 [medline]
PHST- 2002/01/10 10:00 [entrez]
AID - ncb1201-1129 [pii]
AID - 10.1038/ncb1201-1129 [doi]
PST - ppublish
SO  - Nat Cell Biol. 2001 Dec;3(12):1129-32. doi: 10.1038/ncb1201-1129.