| First Author | Neely Kayala KM | Year | 2012 |
| Journal | Brain Res | Volume | 1489 |
| Pages | 8-16 | PubMed ID | 23103503 |
| Mgi Jnum | J:206556 | Mgi Id | MGI:5551370 |
| Doi | 10.1016/j.brainres.2012.10.036 | Citation | Neely Kayala KM, et al. (2012) Presenilin-null cells have altered two-pore calcium channel expression and lysosomal calcium: implications for lysosomal function. Brain Res 1489:8-16 |
| abstractText | 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 gamma-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. |
