Endogenous presenilin 1 redistributes to the surface of lamellipodia upon adhesion of Jurkat cells to a collagen matrix.
Most familial early-onset Alzheimer's disease cases are caused by mutations in the presenilin 1 (PS1) gene. Subcellular localization of the endogenous PS1 is essential for understanding its function, interactions with proteins, and role in Alzheimer's disease. Although numerous studies revealed predominant localization of PS1 to endoplasmic reticulum and Golgi, there are conflicting reports on the localization of PS1 to the cell surface. We found that endogenous PS1 is highly expressed in T lymphocytes (Jurkat cells). Using a variety of methods, we present evidence that endogenous PS1 is localized to the cell surface in addition to intracellular membrane compartments. Moreover, PS1 appeared in high levels on the surface of lamellipodia upon adhesion of the cells to a collagen matrix. The redistribution of PS1 in adhered cells was strikingly similar to that of the well characterized adhesion protein CD44. Cell surface PS1 formed complexes in vivo with actin-binding protein filamin (ABP-280), which is known to form bridges between cell surface receptors and cytoskeleton and mediate cell adhesion and cell motility. Taken together, our results suggest a role of PS1 in cell adhesion and/or cell-matrix interaction.
Department of Psychiatry and Behavioral Sciences, State University of New York at Stony Brook, Stony Brook, NY 11794, USA.
A L
AL
Schwarzman
N
N
Singh
M
M
Tsiper
L
L
Gregori
A
A
Dranovsky
M P
MP
Vitek
C G
CG
Glabe
P H
PH
St George-Hyslop
D
D
Goldgaber
D000465:Algorithms; D000544:Alzheimer Disease; D000595:Amino Acid Sequence; D002448:Cell Adhesion / Q000502:physiology*; D002462:Cell Membrane / Q000502:physiology / Q000648:ultrastructure; D002465:Cell Movement; D003094:Collagen; D016384:Consensus Sequence; D003285:Contractile Proteins / Q000502:physiology; D003593:Cytoplasm / Q000502:physiology / Q000648:ultrastructure; D005109:Extracellular Matrix / Q000502:physiology; D064448:Filamins; D006801:Humans; D018960:Hyaluronan Receptors / Q000502:physiology; D007150:Immunohistochemistry; D019169:Jurkat Cells; D008565:Membrane Proteins / Q000378:metabolism*; D008840:Microfilament Proteins / Q000502:physiology; D008855:Microscopy, Electron, Scanning; D008969:Molecular Sequence Data; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D053764:Presenilin-1; D011948:Receptors, Antigen, T-Cell / Q000502:physiology
D003285:Contractile Proteins; D064448:Filamins; D018960:Hyaluronan Receptors; D008565:Membrane Proteins; D008840:Microfilament Proteins; C508853:PSEN1 protein, human; D019151:Peptide Library; D010455:Peptides; D053764:Presenilin-1; D011948:Receptors, Antigen, T-Cell; D003094:Collagen