A myristoylated calcium-binding protein that preferentially interacts with the Alzheimer's disease presenilin 2 protein.
It is well established that mutations in the presenilin 1 and 2 genes cause the majority of early onset Alzheimer's disease (AD). However, our understanding of the cellular functions of the proteins they encode remains rudimentary. Knowledge of proteins with which the presenilins interact should lead to a better understanding of presenilin function in normal and disease states. We report here the identification of a calcium-binding protein, calmyrin, that interacts preferentially with presenilin 2 (PS2). Calmyrin is myristoylated, membrane-associated, and colocalizes with PS2 when the two proteins are overexpressed in HeLa cells. Yeast two-hybrid liquid assays, affinity chromatography, and coimmunoprecipitation experiments confirm binding between PS2 and calmyrin. Functionally, calmyrin and PS2 increase cell death when cotransfected into HeLa cells. These results allude to several provocative possibilities for a dynamic role of calmyrin in signaling, cell death, and AD.
Stabler
S M
SM
Medical Biotechnology Center and Department of Neurology, University of Maryland, Baltimore, Maryland 21201, USA.
Ostrowski
L L
LL
Janicki
S M
SM
Monteiro
M J
MJ
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000032:analysis / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D002846:Chromatography, Affinity; D003593:Cytoplasm / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D006367:HeLa Cells; D006801:Humans; D008074:Lipoproteins / Q000032:analysis / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000032:analysis / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009227:Myristic Acids / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011233:Precipitin Tests; D053766:Presenilin-2; D011485:Protein Binding; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D015003:Yeasts / Q000235:genetics / Q000378:metabolism
C109198:CIB1 protein, human; D002135:Calcium-Binding Proteins; D008074:Lipoproteins; D008565:Membrane Proteins; D009227:Myristic Acids; C508861:PSEN2 protein, human; D010446:Peptide Fragments; D053766:Presenilin-2; D012333:RNA, Messenger; D002118:Calcium