scholarly journals Calpain Activity Regulates the Cell Surface Distribution of Amyloid Precursor Protein

2002 ◽  
Vol 277 (39) ◽  
pp. 36415-36424 ◽  
Author(s):  
Paul M. Mathews ◽  
Ying Jiang ◽  
Stephen D. Schmidt ◽  
Olivera M. Grbovic ◽  
Marc Mercken ◽  
...  
Keyword(s):  
Cell Surface ◽  
Amyloid Precursor Protein ◽  
Precursor Protein ◽  
Calpain Activity ◽  
Surface Distribution

Intracellular and cell-surface distribution of amyloid precursor protein in cortical astrocytes

1999 ◽  
Vol 50 (1) ◽  
pp. 27-32 ◽  
Author(s):  
Michael J Young ◽  
Robert K.K Lee ◽  
Sonal Jhaveri ◽  
Richard J Wurtman
Keyword(s):  
Cell Surface ◽  
Amyloid Precursor Protein ◽  
Precursor Protein ◽  
Surface Distribution ◽  
Cortical Astrocytes

scholarly journals Amyloid Precursor Protein Enhances Nav1.6 Sodium Channel Cell Surface Expression

2015 ◽  
Vol 290 (19) ◽  
pp. 12048-12057 ◽  
Author(s):  
Chao Liu ◽  
Francis Chee Kuan Tan ◽  
Zhi-Cheng Xiao ◽  
Gavin S. Dawe
Keyword(s):  
Cell Surface ◽  
Amyloid Precursor Protein ◽  
Sodium Channel ◽  
Surface Expression ◽  
Precursor Protein ◽  
Cell Surface Expression

scholarly journals The discrepancy between presenilin subcellular localization and γ-secretase processing of amyloid precursor protein

2001 ◽  
Vol 154 (4) ◽  
pp. 731-740 ◽  
Author(s):  
Philippe Cupers ◽  
Mustapha Bentahir ◽  
Katleen Craessaerts ◽  
Isabelle Orlans ◽  
Hugo Vanderstichele ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Surface ◽  
Amyloid Precursor Protein ◽  
Primary Cultures ◽  
Brefeldin A ◽  
Precursor Protein ◽  
Subcellular Compartment ◽  
Marker Proteins ◽  
Intermediate Compartment ◽  
The Relationship

We investigated the relationship between PS1 and γ-secretase processing of amyloid precursor protein (APP) in primary cultures of neurons. Increasing the amount of APP at the cell surface or towards endosomes did not significantly affect PS1-dependent γ-secretase cleavage, although little PS1 is present in those subcellular compartments. In contrast, almost no γ-secretase processing was observed when holo-APP or APP-C99, a direct substrate for γ-secretase, were specifically retained in the endoplasmic reticulum (ER) by a double lysine retention motif. Nevertheless, APP-C99-dilysine (KK) colocalized with PS1 in the ER. In contrast, APP-C99 did not colocalize with PS1, but was efficiently processed by PS1-dependent γ-secretase. APP-C99 resides in a compartment that is negative for ER, intermediate compartment, and Golgi marker proteins. We conclude that γ-secretase cleavage of APP-C99 occurs in a specialized subcellular compartment where little or no PS1 is detected. This suggests that at least one other factor than PS1, located downstream of the ER, is required for the γ-cleavage of APP-C99. In agreement, we found that intracellular γ-secretase processing of APP-C99-KK both at the γ40 and the γ42 site could be restored partially after brefeldin A treatment. Our data confirm the “spatial paradox” and raise several questions regarding the PS1 is γ-secretase hypothesis.

scholarly journals Amyloid Precursor Protein and Notch Intracellular Domains are Generated after Transport of their Precursors to the Cell Surface

Traffic ◽  
2006 ◽  
Vol 7 (4) ◽  
pp. 408-415 ◽  
Author(s):  
Christoph Kaether ◽  
Stephanie Schmitt ◽  
Michael Willem ◽  
Christian Haass
Keyword(s):  
Cell Surface ◽  
Amyloid Precursor Protein ◽  
Precursor Protein ◽  
Intracellular Domains

A Role for Presenilin 1 in Regulating the Delivery of Amyloid Precursor Protein to the Cell Surface

2002 ◽  
Vol 11 (1) ◽  
pp. 64-82 ◽  
Author(s):  
Jae Yoon Leem ◽  
Carlos A. Saura ◽  
Claus Pietrzik ◽  
John Christianson ◽  
Christian Wanamaker ◽  
...  
Keyword(s):  
Cell Surface ◽  
Amyloid Precursor Protein ◽  
Precursor Protein ◽  
Presenilin 1

scholarly journals Reciprocal Modulation Between Amyloid Precursor Protein and Synaptic Membrane Cholesterol Revealed By Live Cell Imaging

2018 ◽  
Author(s):  
Claire E. DelBove ◽  
Claire E. Strothman ◽  
Roman M. Lazarenko ◽  
Hui Huang ◽  
Charles R. Sanders ◽  
...  
Keyword(s):  
Amyloid Precursor Protein ◽  
Fluorescent Protein ◽  
Dominant Negative ◽  
Precursor Protein ◽  
Membrane Cholesterol ◽  
Synaptic Membrane ◽  
Surface Distribution ◽  
Cholesterol Levels ◽  
App Trafficking ◽  
Green Fluorescent

SummaryThe amyloid precursor protein (APP) has been extensively studied because of its association with Alzheimer’s disease (AD). However, APP distribution across different subcellular membrane compartments and its function in neurons remains unclear. We generated an APP fusion protein with a pH-sensitive green fluorescent protein at its ectodomain and a pH-insensitive blue fluorescent protein at its cytosolic domain and used it to measure APP’s distribution, subcellular trafficking and cleavage in live neurons. This reporter, closely resembling endogenous APP, revealed only a limited correlation between synaptic activities and APP trafficking. However, the synaptic surface distribution of APP was inversely correlated to membrane cholesterol levels, a phenomenon that involves APP’s cholesterol-binding site. Mutations within this site not only altered surface APP and cholesterol levels in a dominant negative manner, but also increased synaptic vulnerability to moderate membrane cholesterol reduction. Our results reveal reciprocal modulation of APP and membrane cholesterol levels at synaptic boutons.

Cell Surface Receptor Function of Amyloid Precursor Protein That Activates Ser/Thr Kinases

Gerontology ◽  
1996 ◽  
Vol 42 (1) ◽  
pp. 2-11 ◽  
Author(s):  
Yoshitake Murayama ◽  
Shizu Takeda ◽  
Kazuyoshi Yonezawa ◽  
Ugo Giambarella ◽  
Ikuo Nishimoto ◽  
...  
Keyword(s):  
Cell Surface ◽  
Amyloid Precursor Protein ◽  
Precursor Protein ◽  
Cell Surface Receptor ◽  
Receptor Function ◽  
Surface Receptor

scholarly journals Specific Biarsenical Labeling of Cell Surface Proteins Allows Fluorescent- and Biotin-tagging of Amyloid Precursor Protein and Prion Proteins

2009 ◽  
Vol 20 (1) ◽  
pp. 233-244 ◽  
Author(s):  
Yuzuru Taguchi ◽  
Zhen-Dan Shi ◽  
Brian Ruddy ◽  
David W. Dorward ◽  
Lois Greene ◽  
...  
Keyword(s):  
Cell Surface ◽  
Amyloid Precursor Protein ◽  
Extracellular Proteins ◽  
Surface Proteins ◽  
Precursor Protein ◽  
Cysteine Protease Inhibitor ◽  
Steric Effects ◽  
Cell Surface Proteins ◽  
Infected Cells ◽  
Fluorescent Tagging

Fluorescent tagging is a powerful tool for imaging proteins in living cells. However, the steric effects imposed by fluorescent tags impair the behavior of many proteins. Here, we report a novel technique, Instant with DTT, EDT, And Low temperature (IDEAL)-labeling, for rapid and specific FlAsH-labeling of tetracysteine-tagged cell surface proteins by using prion protein (PrP) and amyloid precursor protein (APP) as models. In prion-infected cells, FlAsH-labeled tetracysteine-tagged PrP converted from the normal isoform (PrPsen) to the disease-associated isoform (PrPres), suggesting minimal steric effects of the tag. Pulse-chase analysis of PrP and APP by fluorescent gel imaging demonstrated the utility of IDEAL labeling in investigating protein metabolism by identifying an as-yet-unrecognized C-terminal fragment (C3) of PrPsen and by characterizing the kinetics of PrPres and APP metabolism. C3 generation and N-terminal truncation of PrPres were inhibited by the anti-prion compound E64, a cysteine protease inhibitor. Surprisingly, E64 did not inhibit the synthesis of new PrPres, providing insight into the mechanism by which E64 reduces steady-state PrPres levels in prion-infected cells. To expand the versatility of tetracysteine tagging, we created new Alexa Fluor- and biotin-conjugated tetracysteine-binding molecules that were applied to imaging PrP endocytosis and ultrastructural localization. IDEAL-labeling extends the use of biarsenical derivatives to extracellular proteins and beyond microscopic imaging.

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