Overexpression of a COOH-terminal fragment of β-amyloid precursor protein in HeLa cells results in accumulation in a pre-Golgi compartment and generation of an Aβ-like fragment

Sandra L. Kuentzel, Patty A. Gonzalez-DeWhitt, David E. Lowery, Richard A. Altman, Joseph W. Leone, Robert L. Heinrikson, Barry D. Greenberg, Thomas J. Raub

Research output: Contribution to journalArticle

Abstract

The COOH-terminal 103-amino acid segment of human β-amyloid precursor protein (AβPP) was tranfected in HeLa cells to study the effects of its overexpression on its subcellular distribution, accumulation and processing. This AβPP segment contains the intact Aβ sequence near its NH2-terminus. Butyrate-induced overexpression resulted in (1) the production and secretion of a 4.5 kDa Aβ-related peptide that was not detected in media conditioned by the corresponding untransfected cells; (2) the formation of large, cytoplasmic inclusions within the early secretory pathway (pre-Golgi) that were immunoreactive with antibodies to the AβPP COOH-terminal region and/or to the NH2-terminal region of the Aβ domain; and (3) the intracellular accumulation of My 14 and 16 kDa polypeptides that were shown to contain the same AβPP epitopes as the intracellular inclusions. This study shows that a protein with an NH2-terminus similar to the β-secretase product is a suitable α-secretase substrate and that the COOH-terminal proteolytic activity responsible for Aβ peptide production exists early in the cellular secretory pathway.

Original languageEnglish (US)
Pages (from-to)86-99
Number of pages14
JournalAmyloid
Volume3
Issue number2
DOIs
StatePublished - 1996

Keywords

  • Alzheimer's disease
  • Amyloid β-protein
  • Amyloid β-protein transfection
  • Processing

ASJC Scopus subject areas

  • Internal Medicine

Fingerprint Dive into the research topics of 'Overexpression of a COOH-terminal fragment of β-amyloid precursor protein in HeLa cells results in accumulation in a pre-Golgi compartment and generation of an Aβ-like fragment'. Together they form a unique fingerprint.

  • Cite this