Aph-1 interacts at the cell surface with proteins in the active γ-secretase complex and membrane-tethered Notch

Emil M. Hansson, Kia Strömberg, Susanne Bergśtedt, Gang Yu, Jan Näslund, Johan Lundkvist, Urban Lendahl

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

The activity of the γ-secretase complex is critical for the processing of a number of transmembrane proteins, including Notch. Functional γ-secretase activity can be reconstituted from four proteins-presenilin, nicastrin, Pen-2 and Aph-1 -but the role of the individual proteins remains unclear. In this report we describe the cellular localization and protein interactions of Aph-1, with particular regard to Notch receptor processing. We found that Aph-1 is present at the cell surface, where it interacts with Pen-2, the mature forms of presenilin and nicastrin, and full-length Notch. Aph-1 also interacts with a truncated form of Notch, which is a direct substrate for γ-secretase, but not with the Notch intracellular domain. Immunoprecipitation data for Notch and Aph-1 showed that the Notch-containing γ-secretase complexes most likely form a small subset of the total number of γ-secretase complexes. In conclusion, these data demonstrate that Aph-1 is present at the cell surface, presumably in active γ-secretase complexes, and interacts with the Notch receptor, both before and after ligand activation.

Original languageEnglish (US)
Pages (from-to)1010-1020
Number of pages11
JournalJournal of Neurochemistry
Volume92
Issue number5
DOIs
StatePublished - Mar 2005

Fingerprint

Amyloid Precursor Protein Secretases
Membrane Proteins
Notch Receptors
Membranes
Presenilins
Proteins
Processing
Immunoprecipitation
Chemical activation
Ligands
Substrates

Keywords

  • Alzheimer's disease
  • Neurodegenerative disease
  • Nicastrin
  • Presenilin
  • Proteolysis

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Aph-1 interacts at the cell surface with proteins in the active γ-secretase complex and membrane-tethered Notch. / Hansson, Emil M.; Strömberg, Kia; Bergśtedt, Susanne; Yu, Gang; Näslund, Jan; Lundkvist, Johan; Lendahl, Urban.

In: Journal of Neurochemistry, Vol. 92, No. 5, 03.2005, p. 1010-1020.

Research output: Contribution to journalArticle

Hansson, Emil M. ; Strömberg, Kia ; Bergśtedt, Susanne ; Yu, Gang ; Näslund, Jan ; Lundkvist, Johan ; Lendahl, Urban. / Aph-1 interacts at the cell surface with proteins in the active γ-secretase complex and membrane-tethered Notch. In: Journal of Neurochemistry. 2005 ; Vol. 92, No. 5. pp. 1010-1020.
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