Cellular prion protein is implicated in the regulation of local Ca²⁺ movements in cerebellar granule neurons

Abstract

1These authors contributed equally to this study.Abbreviations used: AEQ, aequorin; BSA, bovine serum albumin; CGN, cerebellar granule neurons; CH1, immunoglobulin heavy chain constant region 1; ER, endoplasmic reticulum; GFAP, glial fibrillary acidic protein; HA, hemagglutinin; IB, isolation buffer; KO, knock-out; KRB, Krebs-Ringer buffer; lsCSQ, leader sequence of calsequestrin; mAb, monoclonal antibody; pAb, polyclonal antibody; PBS, phosphatebuffered saline; PM, plasma membrane; PMCA, plasma membrane Ca 2+ -ATPase; PrP, prion protein; SDS, sodium dodecyl-sulphate; SER-CA, sarco-endoplasmic reticulum Ca 2+ -ATPase; SOC, store-operated channels; SOCE, store-operated Ca 2+ entry; STIM, stromal interaction molecule; Tg, transgenic; TSE, transmissible spongiform encephalopathies; VOC, voltage-operated channels; WT, wild-type. AbstractThe cellular prion protein (PrP C ) is a cell-surface glycoprotein mainly expressed in the CNS. The structural conversion of PrP C generates the prion, the infectious agent causing

The role of prion protein in stem cell regulation

“…Interestingly, it has been described that PrP C mediates neuronal iron uptake and transport, which is important to keep the brain in working order (Singh et al 2009). It was also reported that PrP C has a high expression at synapses and that it was involved in the homeostasis of Ca 2C of cerebellar granule neurons (Lazzari et al 2011). It can bind copper as well for an antioxidant activity, which, in turn, might have vital implications for synaptic homeostasis (Brown 2001).…”

A novel Ca2+-mediated cross-talk between endoplasmic reticulum and acidic organelles: Implications for NAADP-dependent Ca2+ signalling

“…The ER-Aeq Ca 2+ probe was described in [40]. For generation of the CathD-Aeq Ca 2+ probe a fragment of the cathepsin D (CathD) cDNA was first amplified using the following primers: Forward: 5 -ggaagcttgaattcgccaccatgcagccctccag-3 Reverse: 5 -ggaagcttgagggtcttcccggcctgcgacacct-3 which caused the addition of a HindIII site in the 5 non-coding region and downstream the lysosomal targeting sequence of the CathD cDNA, but not the catalytic region [41].…”

Astrocyte signaling and neurodegeneration

“…As a consequence, the loss of its function, during disease progression, may contribute to Ca 2+ derangement and synaptic failure. 110 Even though astrocytes were described to be the earliest site of PrP Sc accumulation in brain, 111 no information is currently available on the Ca 2+ signaling of scrapie-infected astroglia. The presence of chronically activated glial cells around PrP Sc depositions is a well documented feature in prion diseases.…”