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 protein s, and role in Alzheimer's disease, Although numerous studies revealed pred ominant localization of PSI to endoplasmic reticulum and Golgi, there are c onflicting reports on the localization of PS1 to the cell surface. We found that endogenous PS1 is highly expressed in T lymphocytes (Jurkat cells). U sing a variety of methods, we present evidence that endogenous PSI is local ized 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 a dhered cells was strikingly similar to that of the well characterized adhes ion protein CD44, Cell surface-PS1 formed complexes in vivo with actin-bind ing protein filamin (ABP-280), which is known to form bridges between cell surface receptors and cytoskeleton and mediate cell adhesion and cell motil ity. Taken together, our results suggest a role of PSI in cell adhesion and /or cell-matrix interaction.