Presenilin-1 inhibits delta-catenin-induced cellular branching and promotes delta-catenin processing and turnover

Biochem Biophys Res Commun. 2006 Dec 29;351(4):903-8. doi: 10.1016/j.bbrc.2006.10.135. Epub 2006 Nov 2.

Abstract

Although delta-catenin/neural plakophilin-related armadillo protein (NPRAP) was reported to interact with presenilin-1 (PS-1), the effects of PS-1 on delta-catenin have not been established. In this study, we report that overexpression of PS-1 inhibits the delta-catenin-induced dendrite-like morphological changes in NIH 3T3 cells and promotes delta-catenin processing and turnover. The effects of PS-1 on endogenous delta-catenin processing were confirmed in hippocampal neurons overexpressing PS-1, as well as in the transgenic mice expressing the disease-causing mutant PS-1 (M146V). In addition, disease-causing mutant PS-1 (M146V and L286V) enhanced delta-catenin processing, whereas PS-1/gamma-secretase inhibitors could block the formation of processed forms of delta-catenin. Together, our findings suggest that PS-1 can affect delta-catenin-induced morphogenesis possibly through the regulation of its processing and stability.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / enzymology
  • Alzheimer Disease / genetics
  • Amyloid Precursor Protein Secretases / antagonists & inhibitors
  • Animals
  • Catenins
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism*
  • Dendrites / enzymology
  • Dendrites / ultrastructure*
  • Enzyme Inhibitors / pharmacology
  • Fibroblasts / enzymology
  • Hippocampus / cytology
  • Hippocampus / enzymology
  • Mice
  • Mice, Transgenic
  • NIH 3T3 Cells
  • Neurons / metabolism
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism*
  • Presenilin-1 / antagonists & inhibitors
  • Presenilin-1 / genetics
  • Presenilin-1 / metabolism*
  • Transcriptional Activation

Substances

  • Catenins
  • Cell Adhesion Molecules
  • Enzyme Inhibitors
  • Phosphoproteins
  • Presenilin-1
  • delta catenin
  • Amyloid Precursor Protein Secretases