We now know that the prion protein (PrP) is indisputably involved in the pathogenesis of prion disease. However, despite the many attributed functions, the role of PrP in the cell is still obscure. This issue is further complicated by the lack of obvious phenotypes of PrP-KO mice. Several reports suggest a close link between PrP and the control of Ca2+ homeostasis. Ca2+, the most important second messenger, features in multiple processes, including those that govern the survival and death of the cell. We have addressed the putative Ca2+–PrP connection by analysing local Ca2+ homeostasis in different cell domains, using cerebellar granule cells derived from wild-type and PrP-KO congenic mice, and genetically-targeted recombinant Ca2+-sensitive photo-proteins (aequorins). We have found that, compared to wild-type neurons, the lack of PrP affects all measured Ca2+ movements, i.e. in the cytosolic domains of the plasma membrane, in the lumen of the endoplasmic reticulum and in the mitochondrial matrix. Also, PrP can affect the expression of a series of proteins involved in Ca2+ handling. Thus, taken together, these results substantiate the hypothesis that Ca2+ may act as common denominator for several PrP roles, and that deregulation of the Ca2+ signaling may be crucial in the pathogenesis of prion disease.

The control of Ca2+ metabolism may underlie the multi-faceted attributes of the prion protein

LAZZARI, CRISTIAN;PEGGION, CATERINA;MASSIMINO, MARIA LINA;BERTOLI, ALESSANDRO;SORGATO, MARIA CATIA
2010

Abstract

We now know that the prion protein (PrP) is indisputably involved in the pathogenesis of prion disease. However, despite the many attributed functions, the role of PrP in the cell is still obscure. This issue is further complicated by the lack of obvious phenotypes of PrP-KO mice. Several reports suggest a close link between PrP and the control of Ca2+ homeostasis. Ca2+, the most important second messenger, features in multiple processes, including those that govern the survival and death of the cell. We have addressed the putative Ca2+–PrP connection by analysing local Ca2+ homeostasis in different cell domains, using cerebellar granule cells derived from wild-type and PrP-KO congenic mice, and genetically-targeted recombinant Ca2+-sensitive photo-proteins (aequorins). We have found that, compared to wild-type neurons, the lack of PrP affects all measured Ca2+ movements, i.e. in the cytosolic domains of the plasma membrane, in the lumen of the endoplasmic reticulum and in the mitochondrial matrix. Also, PrP can affect the expression of a series of proteins involved in Ca2+ handling. Thus, taken together, these results substantiate the hypothesis that Ca2+ may act as common denominator for several PrP roles, and that deregulation of the Ca2+ signaling may be crucial in the pathogenesis of prion disease.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11577/2418856
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