Calsenilin: a calcium-binding protein that interacts with the presenilins and regulates the levels of a presenilin fragment.
Most early-onset familial Alzheimer disease (AD) cases are caused by mutations in the highly related genes presenilin 1 (PS1) and presenilin 2 (PS2). Presenilin mutations produce increases in beta-amyloid (Abeta) formation and apoptosis in many experimental systems. A cDNA (ALG-3) encoding the last 103 amino acids of PS2 has been identified as a potent inhibitor of apoptosis. Using this PS2 domain in the yeast two-hybrid system, we have identified a neuronal protein that binds calcium and presenilin, which we call calsenilin. Calsenilin interacts with both PS1 and PS2 in cultured cells, and can regulate the levels of a proteolytic product of PS2. Thus, calsenilin may mediate the effects of wild-type and mutant presenilins on apoptosis and on Abeta formation. Further characterization of calsenilin may lead to an understanding of the normal role of the presenilins and of the role of the presenilins in Alzheimer disease.
Buxbaum
J D
JD
Department of Psychiatry, Mount Sinai School of Medicine, New York, New York 10029, USA. buxbaj01@doc.mssm.edu
Choi
E K
EK
Luo
Y
Y
Lilliehook
C
C
Crowley
A C
AC
Merriam
D E
DE
Wasco
W
W
D017668:Age of Onset; D000544:Alzheimer Disease; D000595:Amino Acid Sequence; D017209:Apoptosis; D002135:Calcium-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D003001:Cloning, Molecular / Q000379:methods; D005136:Eye Proteins; D051597:Hippocalcin; D006801:Humans; D051605:Kv Channel-Interacting Proteins; D008074:Lipoproteins; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments / Q000378:metabolism; D053764:Presenilin-1; D053766:Presenilin-2; D011485:Protein Binding; D051603:Recoverin; D012097:Repressor Proteins; D012441:Saccharomyces cerevisiae / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D014162:Transfection
D002135:Calcium-Binding Proteins; D005136:Eye Proteins; C496749:KCNIP3 protein, human; D051605:Kv Channel-Interacting Proteins; D008074:Lipoproteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C508853:PSEN1 protein, human; C508861:PSEN2 protein, human; D010446:Peptide Fragments; D053764:Presenilin-1; D053766:Presenilin-2; C496731:RCVRN protein, human; D012097:Repressor Proteins; D051603:Recoverin; D051597:Hippocalcin