Abstract：
:Mutations in the presenilin 1 (PS1) gene are associated with autosomal dominant, early-onset, familial Alzheimer's disease and result in increased release of the hyperaggregatable 42-amino acid form of the amyloid beta-peptide (A(beta)42). To determine which subcellular compartments are potential source(s) of released Abeta42, we compared the levels and spatial segregation of intracellular A(beta)40 and A(beta)42 peptides between N2a neuroblastoma cells doubly transfected with the "Swedish" familial Alzheimer's disease-linked amyloid precursor protein variant and either wild-type PS1 (PS1(wt)) or familial Alzheimer's disease-linked delta9 mutant PS1 (PS1delta9). As expected, PS1delta9-expressing cells had dramatically higher levels of intracellular Abeta42 than did cells expressing PS1wt. However, the highest levels of A(beta)42 colocalized not with endoplasmic reticulum or Golgi markers but with rab8, a marker for trans-Golgi network (TGN)-to-plasma membrane (PM) transport vesicles. We show that PS1 mutants are capable of causing accumulation of A(beta)42 in late compartments of the secretory pathway, generating there a readily releasable source of A(beta)42. Our findings indicate that PS1 "bioactivity" localizes to the vicinity of the TGN and/or PM and reconcile the apparent discrepancy between the preponderant concentration of PS1 protein in proximal compartments of the secretory pathway and the recent findings that PS1 "bioactivity" can control gamma-secretase-like processing of another transmembrane substrate, Notch, at or near the PM.
journal_name
J Neurochemjournal_title
Journal of neurochemistryauthors
Petanceska SS,Seeger M,Checler F,Gandy Sdoi
10.1046/j.1471-4159.2000.0741878.xkeywords:
subject
Has Abstractpub_date
2000-05-01 00:00:00pages
1878-84issue
5eissn
0022-3042issn
1471-4159journal_volume
74pub_type
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journal_title：Journal of neurochemistry
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pub_type： 杂志文章
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pub_type： 杂志文章
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更新日期：1992-09-01 00:00:00
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journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2009.06436.x
更新日期：2010-01-01 00:00:00
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更新日期：2014-08-01 00:00:00
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更新日期：1995-01-01 00:00:00
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journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2006.03791.x
更新日期：2006-04-01 00:00:00
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journal_title：Journal of neurochemistry
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doi：10.1111/j.1471-4159.1980.tb07103.x
更新日期：1980-10-01 00:00:00
abstract：:Nuclei from the cerebral cortices of animals of different ages were separated into neuronal and neuroglial populations. Nuclei from cerebellar neurons were also studied. Using the enzyme micrococcal nuclease as a probe for chromatin structure, we found that the DNA from both neuronal preparations showed a decreased su...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1983.tb04769.x
更新日期：1983-08-01 00:00:00
abstract：:In this study, we show specific intracellular responses evoked by the stimulation of astrocytes with the P1,P5-di(adenosine-5')pentaphosphate, Ap5A. The stimulation of astrocytes with micromolar concentrations of the dinucleotide elicited rapid increases in intracellular calcium concentration ([Ca2+]i), showing an EC5...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.2002.01111.x
更新日期：2002-10-01 00:00:00
