Ca2+-independent binding and cellular expression profiles question a significant role of calmyrin in transduction of Ca2+-signals to Alzheimer's disease-related presenilin 2 in forebrain.
The interaction between the EF-hand Ca(2+)-binding protein calmyrin and presenilin 2 (PS2) has been suggested to play a role in Alzheimer's disease (AD). We now report that calmyrin binds specifically endogenous PS2 and not PS1. However, binding appears to be Ca(2+)-independent and calmyrin does not exhibit a Ca(2+)-dependent translocation to intracellular membranes as demonstrated in a Ca(2+)-myristoyl switch assay. Moreover, calmyrin is only present at very low levels in brain areas associated with the onset of AD. In rat, forebrain calmyrin is localized only in a subset of principal neurons, similarly as in human forebrain. Finally, subcellular fractionation demonstrates only a limited overlap of calmyrin and PS2 at neuronal membranes. We therefore conclude that calmyrin will not contribute significantly as a Ca(2+)-sensor that transduces Ca(2+)-signaling events to PS2 in forebrain.
Blazejczyk
Magdalena
M
Laboratory of Neurodegeneration, International Institute of Molecular and Cell Biology, Trojdena 4, 02-109 Warsaw, Poland.
Wojda
Urszula
U
Sobczak
Adam
A
Spilker
Christina
C
Bernstein
Hans-Gert
HG
Gundelfinger
Eckart D
ED
Kreutz
Michael R
MR
Kuznicki
Jacek
J
D000544:Alzheimer Disease / Q000378:metabolism*; D000818:Animals; D019556:COS Cells; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002522:Chlorocebus aethiops; D020869:Gene Expression Profiling; D006367:HeLa Cells; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D053766:Presenilin-2; D016548:Prosencephalon / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D011993:Recombinant Fusion Proteins / Q000378:metabolism
D002135:Calcium-Binding Proteins; C491604:Cib1 protein, rat; D008565:Membrane Proteins; C508861:PSEN2 protein, human; D053766:Presenilin-2; D011993:Recombinant Fusion Proteins; D002118:Calcium