Characterization of Detergent-Insoluble Complexes Containing the Familial Alzheimer's Disease-Associated Presenilins.

Parkin, Edward T. and Hussain, Ishrut and Karran, Eric H. and Turner, Anthony J. and Hooper, Nigel M. (1999) Characterization of Detergent-Insoluble Complexes Containing the Familial Alzheimer's Disease-Associated Presenilins. Journal of Neurochemistry, 72 (4). pp. 1534-1543. ISSN 0022-3042

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Abstract

Many cases of early-onset familial Alzheimer’s disease have been linked to mutations within two genes encoding the proteins presenilin-1 and presenilin-2. The presenilins are 48-56-kDa proteins that can be proteolytically cleaved to generate an N-terminal fragment (25-35 kDa) and a C-terminal fragment (17-20 kDa). The N- and C-terminal fragments of presenilin-1, but not full-length presenilin-1, were readily detected in both human and mouse cerebral cortex and in neuronal and glioma cell lines. In contrast, presenilin-2 was detected almost exclusively in cerebral cortex as the full-length molecule with a molecular mass of 56 kDa. The association of the presenilins with detergent-insoluble, low-density membrane microdomains, following the isolation of these structures from cerebral cortex by solubilization in Triton X-100 and subsequent sucrose density gradient centrifugation, was also examined. A minor fraction (10%) of both the N- and C-terminal fragments of presenilin-1 was associated with the detergent-insoluble, low-density membrane microdomains, whereas a considerably larger proportion of full-length presenilin-2 was present in the same membrane microdomains. In addition, a significant proportion of full-length presenilin-2 was present in a high-density, detergent-insoluble cytoskeletal pellet enriched in β-actin. The presence of the presenilins in detergent-insoluble, low-density membrane microdomains indicates a possible role for these specialized regions of the membrane in the lateral separation of Alzheimer’s disease-associated proteins within the lipid bilayer and/or in the distinct functions of these proteins.

Item Type:
Journal Article
Journal or Publication Title:
Journal of Neurochemistry
Uncontrolled Keywords:
/dk/atira/pure/researchoutput/libraryofcongress/qh301
Subjects:
ID Code:
9456
Deposited By:
Deposited On:
11 Jun 2008 09:29
Refereed?:
Yes
Published?:
Published
Last Modified:
07 Jan 2020 02:58