Presenilin-1 inhibits delta-catenin-induced cellular branching and promotes delta-catenin processing and turnover.
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.
Kim
Jin-Sook
JS
The College of Pharmacy, Chonnam National University, Gwangju, Republic of Korea.
Bareiss
Sonja
S
Kim
Kyung Keun
KK
Tatum
Rodney
R
Han
Jeong-Ran
JR
Jin
Yun Hye
YH
Kim
Hangun
H
Lu
Qun
Q
Kim
Kwonseop
K
D000544:Alzheimer Disease / Q000201:enzymology / Q000235:genetics; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors; D000818:Animals; D051177:Catenins; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D003712:Dendrites / Q000201:enzymology / Q000648:ultrastructure*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000201:enzymology; D006624:Hippocampus / Q000166:cytology / Q000201:enzymology; D051379:Mice; D008822:Mice, Transgenic; D041681:NIH 3T3 Cells; D009474:Neurons / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D053764:Presenilin-1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D000095002:Delta Catenin
D051177:Catenins; D015815:Cell Adhesion Molecules; D004791:Enzyme Inhibitors; D010750:Phosphoproteins; D053764:Presenilin-1; D053829:Amyloid Precursor Protein Secretases; D000095002:Delta Catenin; C000722350:Ctnnd2 protein, mouse