Calsenilin: A calcium-binding protein that interacts with the presenilins and regulates the levels of a presenilin fragment

@article{Buxbaum1998CalsenilinAC,
  title={Calsenilin: A calcium-binding protein that interacts with the presenilins and regulates the levels of a presenilin fragment},
  author={Joseph D. Buxbaum and Eun-Kyoung Choi and Yuxia Luo and Christina Lilliehook and Annette C. Crowley and David E. Merriam and Wilma Wasco},
  journal={Nature Medicine},
  year={1998},
  volume={4},
  pages={1177-1181}
}
Most early-onset familial Alzheimer disease (AD) cases are caused by mutations in the highly related genes presenilin 1 (PS1) and presenilin 2 (PS2). Presenilin mutations produce increases in ß-amyloid (Aß) formation and apoptosis in many experimental systems. A cDNA (ALG-3) encoding the last 103 amino acids of PS2 has been identified as a potent inhibitor of apoptosis. Using this PS2 domain in the yeast two-hybrid system, we have identified a neuronal protein that binds calcium and presenilin… 
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TLDR
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TLDR
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TLDR
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TLDR
It is shown that overexpression of wild-type PS2 or PS2 mutant containing the FAD mutation N141I (PS2mut) in various cell lines inhibits the synthesis of coexpressed reporter and endogenous proteins and suggests that presenilins may function as regulators of protein synthesis.
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TLDR
This review will discuss the components of the γ-secretase complex and the role of presenilin interacting proteins on ιsecretase activity.
The roles of presenilin and FKBP14 in Drosophila development and Notch signalling.
TLDR
It is demonstrated that an immunosuppressant drug known as FK506, which binds FKBPs and abrogates their function, reduced Psn, anterior pharynx defective 1 and presenilin enhancer 2 protein levels in vivo.
γ-Secretase Activity of Presenilin 1 Regulates Acetylcholine Muscarinic Receptor-mediated Signal Transduction*
TLDR
The findings suggest that PS1 can regulate PLC activity and that this function is γ-secretase activity-dependent, and the mechanisms by which PS1 interferes with PLC-calcium signaling are elucidated.
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References

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Interaction of Presenilins with the Filamin Family of Actin-Binding Proteins
TLDR
It is reported here that the loop regions of PS1 and PS2 interact with nonmuscle filamin and a structurally related protein (filamin homolog 1, Fh1) and that interactions between presenilins and ABP280/Fh1 may be functionally significant.
The presenilins and Alzheimer's disease.
TLDR
The presenilin data provide independent support for the amyloid cascade hypothesis of Alzheimer's pathogenesis and work on the Caenorhabditis elegans homologues of thepresenilins suggests that the presenILins may have a more general and direct role in the processing and trafficking of membrane-bound proteins and that, in part, the pathogenic mutations may disrupt this role.
Calbindin D28k blocks the proapoptotic actions of mutant presenilin 1: reduced oxidative stress and preserved mitochondrial function.
TLDR
It is reported that overexpression of the calcium-binding protein calbindin D28k prevents apoptosis in cultured neural cells expressing mutant PS-1 (L286V and M146V missense mutations), which suggests that PS- 1 mutations render neurons vulnerable to apoptosis by a mechanism involving destabilization of cellular calcium homeostasis, which leads to oxidative stress and mitochondrial dysfunction.
Endoproteolytic Cleavage and Proteasomal Degradation of Presenilin 2 in Transfected Cells*
TLDR
Using a stably transfected, inducible cell system, it is found that PS2 is proteolytically cleaved into two stable cellular polypeptides including an ∼20-kDa C-terminal fragment and an ∼34-k da N-terminals fragment.
The presenilin 2 loop domain interacts with the mu-calpain C-terminal region.
TLDR
Results suggested that PS2 and mu-calpain interact with each other, and might regulate each other's functions.
Evidence That Levels of Presenilins (PS1 and PS2) Are Coordinately Regulated by Competition for Limiting Cellular Factors*
TLDR
It is revealed that compromised accumulation of murine PS1 and PS2 derivatives resulting from overexpression of human PS1 occurs in a manner independent of endoproteolytic cleavage, consistent with a model in which the abundance of PS2 fragments is regulated coordinately by competition for limiting cellular factor(s).
Presenilin 1 interaction in the brain with a novel member of the Armadillo family
TLDR
In the non-neuronal 293 cell line, PS1 interacted with β-catenin, the family member with the greatest homology to Armadillo, which interacts with PS1 and is principally expressed in brain.
Alternative cleavage of Alzheimer-associated presenilins during apoptosis by a caspase-3 family protease.
TLDR
In cells expressing PS2 containing the asparagine-141 FAD mutant, the ratio of alternative to normal PS2 cleavage fragments was increased relative to wild-type PS2-expressing cells, suggesting a potential role for apoptosis-associated cleavage of presenilins in the pathogenesis of Alzheimer's disease.
Increased Sensitivity to Mitochondrial Toxin-Induced Apoptosis in Neural Cells Expressing Mutant Presenilin-1 Is Linked to Perturbed Calcium Homeostasis and Enhanced Oxyradical Production
TLDR
The data suggest that by perturbing subcellular calcium homeostasis presenilin mutations sensitize neurons to mitochondria-based forms of apoptosis that involve oxidative stress.
Presenilins Are Processed by Caspase-type Proteases*
TLDR
Studying the cleavage of PS1 and PS2 in transiently and stably transfected hamster kidney and mouse and human neuroblastoma cells by immunoblot and pulse-chase experiments confirmed the involvement of caspase(s).
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