Presenilin-null cells have altered two-pore calcium channel expression and lysosomal calcium: implications for lysosomal function.

Autor: Neely Kayala KM; Department of Neurobiology and Behavior, University of California, Irvine, 3208 Biological Sciences III, Irvine, CA 92697-4545, United States., Dickinson GD, Minassian A, Walls KC, Green KN, Laferla FM
Jazyk: angličtina
Zdroj: Brain research [Brain Res] 2012 Dec 13; Vol. 1489, pp. 8-16. Date of Electronic Publication: 2012 Oct 24.
DOI: 10.1016/j.brainres.2012.10.036
Abstrakt: Presenilins are necessary for calcium homeostasis and also for efficient proteolysis through the autophagy/lysosome system. Presenilin regulates both endoplasmic reticulum calcium stores and autophagic proteolysis in a γ-secretase independent fashion. The endo-lysosome system can also act as a calcium store, with calcium efflux channels being recently identified as two-pore channels 1 and 2. Here we investigated lysosomal calcium content and the channels that mediate calcium release from these acidic stores in presenilin knockout cells. We report that presenilin loss leads to a lower total lysosomal calcium store despite the buildup of lysosomes found in these cells. Additionally, we find alterations in two-pore calcium channel protein expression, with loss of presenilin preventing the formation of a high molecular weight species of TPC1 and TPC2. Finally, we find that treatments that disturb lysosomal calcium release lead to a reduction in autophagy function yet lysosomal inhibitors do not alter two-pore calcium channel expression. These data indicate that alterations in lysosomal calcium in the absence of presenilins might be leading to disruptions in autophagy.
(Copyright © 2012 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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