Presenilin 1 is involved in maturation and trafficking of N-cadherin to the plasma membrane.
One pathological characteristic of Alzheimer's disease (AD) is extensive synapse loss. Presenilin 1 (PS1) is linked to the pathogenesis of early onset familial Alzheimer's disease (FAD) and is localized at the synapse, where it binds N-cadherin and modulates its adhesive activity. To elucidate the role of the PS1/N-cadherin interaction in synaptic contact, we established SH-SY5Y cells stably expressing wild-type (wt) PS1 and dominant-negative (D385A) PS1. We show that the formation of cadherin-based cell-cell contact among SH-SY5Y cells stably expressing D385A PS1 was suppressed. Conversely, wt PS1 cells exhibited enhanced cell-cell contact and colony formation. Suppression of cell-cell contact in D385A cells was accompanied by an alteration in N-cadherin subcellular localization; N-cadherin was retained mainly in the endoplasmic reticulum (ER) and cell surface expression was reduced. We conclude that PS1 is essential for efficient trafficking of N-cadherin from the ER to the plasma membrane. PS1-mediated delivery of N-cadherin to the plasma membrane is important for N-cadherin to exert its physiological function, and it may control the state of cell-cell contact.
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D001921:Brain / Q000378:metabolism / Q000503:physiopathology; D015820:Cadherins / Q000378:metabolism*; D002448:Cell Adhesion / Q000235:genetics*; D002449:Cell Aggregation / Q000235:genetics; D002450:Cell Communication / Q000235:genetics; D002460:Cell Line; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006801:Humans; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics; D008970:Molecular Weight; D009154:Mutation / Q000235:genetics; D053764:Presenilin-1; D017729:Presynaptic Terminals / Q000378:metabolism* / Q000473:pathology; D011485:Protein Binding / Q000235:genetics; D021381:Protein Transport / Q000235:genetics; D013570:Synaptic Membranes / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D051176:beta Catenin
C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D046911:Macromolecular Substances; D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1; D015534:Trans-Activators; D051176:beta Catenin