Identification of the presenilins in hematopoietic cells with localization of presenilin 1 to neutrophil and platelet granules.
Most cases of familial Alzheimer disease (AD) are caused by mutations in presenilin 1 (PS1) and presenilin 2 (PS2). Presenilins are required for the proteolytic processing of the beta amyloid precursor protein, which yields beta amyloid peptide, the major component of extracellular amyloid plaques. In addition, presenilins are essential for proteolytic processing of other membrane proteins, including Notch, TrkB, and APLP2. Notch directs neural and hematopoietic development. Here we show mRNA and protein expression of PS1 in both lymphoid and myeloid cells, while PS2 mRNA is present only in lymphocytes. Expression of PS1 was found throughout myeloid development from CD34+ stem cells to platelets and neutrophils. PS1 expression was found in avian as well as mammalian blood cells. In neutrophils, PS1 colocalized with myeloperoxidase and CD63 within the azurophil granules as demonstrated by subcellular fractionation and double labeling immunogold electron microscopy. In platelets, PS1 colocalized with glucose transporter (GLUT-3) in the membrane of alpha granules, as evidenced by immunogold electron microscopy. The colocalization of PS1 and amyloid precursor protein in cell-specific granules suggests a conserved function across different tissues. These studies indicate that PS1 may play multiple roles in blood cell physiology and that blood tissue may provide a model to study PS1 interactions with other proteins.
Mirinics
Zeljka Korade
ZK
Department of Pediatrics, University of Pittsburgh School of Medicine, Pennsylvania 15261, USA. zkorade@pitt.edu
Calafat
Jero
J
Udby
Lene
L
Lovelock
Josh
J
Kjeldsen
Lars
L
Rothermund
Kristi
K
Sisodia
Sangram S
SS
Borregaard
Niels
N
Corey
Seth J
SJ
D000328:Adult; D000818:Animals; D001792:Blood Platelets / Q000737:chemistry* / Q000648:ultrastructure; D002458:Cell Fractionation; D002645:Chickens; D003594:Cytoplasmic Granules / Q000737:chemistry*; D006412:Hematopoietic Stem Cells / Q000737:chemistry*; D006801:Humans; D008214:Lymphocytes / Q000737:chemistry; D008565:Membrane Proteins / Q000378:metabolism* / Q000502:physiology; D008854:Microscopy, Electron; D022423:Myeloid Cells / Q000737:chemistry; D009504:Neutrophils / Q000737:chemistry* / Q000648:ultrastructure; D053764:Presenilin-1; D053766:Presenilin-2; D012333:RNA, Messenger / Q000378:metabolism; D014407:Tumor Cells, Cultured
D008565:Membrane Proteins; C508853:PSEN1 protein, human; C508861:PSEN2 protein, human; D053764:Presenilin-1; D053766:Presenilin-2; D012333:RNA, Messenger