Presenilin-1 forms complexes with the cadherin/catenin cell-cell adhesion system and is recruited to intercellular and synaptic contacts

In MDCK cells, presenilin-1 (PS1) accumulates at intercellular contacts whe re it colocalizes with components of the cadherin-based adherens junctions. PS1 fragments form complexes with E-cadherin, beta-catenin, and alpha-cate nin, all components of adherens junctions. In confluent MDCK cells, PS1 for ms complexes with cell surface E-cadherin; disruption of Ca2+-dependent cel l-cell contacts reduces surface PS1 and the levels of PS1-E-cadherin comple xes. PS1 overexpression in human kidney cells enhances cell-cell adhesion. Together, these data show that PS1 incorporates into the cadherin/catenin a dhesion system and regulates cell-cell adhesion. PS1 concentrates at interc ellular contacts in epithelial tissue; in brain, it forms complexes with bo th E- and N-cadherin and concentrates at synaptic adhesions. That PS1 is a constituent of the cadherin/catenin complex makes that complex a potential target for PS1 FAD mutations.