Facilitation of lin-12-mediated signalling by sel-12, a Caenorhabditis elegans S182 Alzheimer's disease gene

Levitan, Diane; Greenwald, Iva

doi:10.1038/377351a0

Cited by 685 publications

(456 citation statements)

References 29 publications

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“…The existence of a moderate but significant amino acid similarity between the presenilins and spe4, a Caenorhabditis elegans gene involved in the transport and partitioning of cellular constituents during spermatogenes~s, has led to the proposal that the presenilins might participate in intracellular protein transport [1]. Homology with another C. elegans gene sell2 (48% amino acid similarity), which facilitates signalling mediated by lin 12/Notch, suggested that the presenilins might be involved in the transduction pathway of the linl2/Notch family [7].…”

Section: Introductionmentioning

confidence: 99%

Immunohistochemical analysis of presenilin‐1 expression in the mouse brain

et al. 1996

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). In order to study the localization of PS-1 in the brain, we raised a polyclonal antiserum specific to a fragment of the predicted protein sequence of PS-1. PS-1 immunostaining was found intracellulady, in the perikaria of discrete cells, mostly neurons, appearing as thick granules, resembling large-size vesicles. These granules were located in the periphery of cell bodies and extended into dendrites and neurites. PS-1 expression was found to be broadly distributed throughout the mouse brain, not only in structures involved in AD pathology, but also in structures unaltered by this di~ense.

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Section: Introductionmentioning

confidence: 99%

Immunohistochemical analysis of presenilin‐1 expression in the mouse brain

et al. 1996

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“…In addition, two mutations were described in a similar gene (67% homologous to PS1), named STM-2, E5-1 or PS2 located on chromosome l [9,10]. The predicted amino acid se-quence encoded in the longest open reading frame composed of 10 exons [7] reveals high similarities with the Caernorhabditis elegans protein SEL-12 [11]. SEL-12 facilitates LIN-12 mediated cell signalling via the Notch family of receptors during development of C elegans.…”

Section: Introductionmentioning

confidence: 99%

Alzheimer's presenilin 1 gene expression in platelets and megakaryocytes

Vidal¹,

Ghiso²,

Wısnıewskı³

et al. 1996

FEBS Letters

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The presenilin 1 (PSI) gene located on chromosome 14 has been linked with the majority of early-onset FAD. The normal biological role of PS1 as well as the mechanism by which mutations in PSI cause FAD remains unknown. PSI expression in platelets and the Dami megakaryocytic cell line was examined by Western blot analysis and RT-PCR. Using an anti-Nterminus PS1 antibody we detected PSI immunoreactive bands of 44, 32 and 27 kDa in both cell types. After RT-PCR we observed that platelets and megakaryocytes carry at least four different PSI transcripts. One of them is a novel PSI splice variant that lacks the coding sequence for exon 10 resulting in a shorter 409 amino acid protein.

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“…The biological function of the presenilins remains essentially unknown, but, interestingly, the 103 carboxyl-terminal amino acid residues of PS2 can inhibit apoptosis in a "deathtrap" assay (18). Based on the homology with Caenorhabditis elegans proteins, roles in intracellular protein sorting and/or intercellular signal transmission have been proposed as well (19,20).…”

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confidence: 99%

Phosphorylation, Subcellular Localization, and Membrane Orientation of the Alzheimer's Disease-associated Presenilins

Strooper¹,

Beullens²,

Contreras

et al. 1997

Journal of Biological Chemistry

272

187

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Presenilins 1 and 2 are unglycosylated proteins with apparent molecular mass of 45 and 50 kDa, respectively, in transfected COS-1 and Chinese hamster ovary cells. They colocalize with proteins from the endoplasmic reticulum and the Golgi apparatus in transfected and untransfected cells. In COS-1 cells low amounts of intact endogeneous presenilin 1 migrating at 45 kDa are detected together with relative larger amounts of presenilin 1 fragments migrating between 18 and 30 kDa. The presenilins have a strong tendency to form aggregates (mass of 100 -250 kDa) in SDS-polyacrylamide gel electrophoresis, which can be partially resolved when denatured by SDS at 37°C instead of 95°C. Sulfation, glycosaminoglycan modification, or acylation of the presenilins was not observed, but both proteins are posttranslationally phosphorylated on serine residues. The mutations Ala-246 3 Glu or Cys-410 3 Tyr that cause Alzheimer's disease do not interfere with the biosynthesis or phosphorylation of presenilin 1. Finally, using low concentrations of digitonin to selectively permeabilize the cell membrane but not the endoplasmic reticulum membrane, it is demonstrated that the two major hydrophilic domains of presenilin 1 are oriented to the cytoplasm. The current investigation documents the posttranslational modifications and subcellular localization of the presenilins and indicates that postulated interactions with amyloid precursor protein metabolism should occur in the early compartments of the biosynthetic pathway.

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Facilitation of lin-12-mediated signalling by sel-12, a Caenorhabditis elegans S182 Alzheimer's disease gene

Cited by 685 publications

References 29 publications

Immunohistochemical analysis of presenilin‐1 expression in the mouse brain

Immunohistochemical analysis of presenilin‐1 expression in the mouse brain

Alzheimer's presenilin 1 gene expression in platelets and megakaryocytes

Phosphorylation, Subcellular Localization, and Membrane Orientation of the Alzheimer's Disease-associated Presenilins

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