Subcellular localization and dimerization of APLP1 are strikingly different from APP and APLP2

• DOI: 10.1242/jcs.034058
• Publication Date: 2009-01-07T03:18:40Z
• Authors: Daniela Kaden; Philipp Voigt; Lisa-Marie Munter; Karolina D. Bobowski; Michael Schaefer; Gerd Multhaup
• Keywords: Ectodomain

The molecular association between APP and its mammalian homologs has hardly been explored. In systematically addressing this issue, we show by live cell imaging that APLP1 mainly localizes to the surface, whereas APLP2 are mostly found in intracellular compartments. Homo- heterotypic cis interactions of family members could be detected FRET co-immunoprecipitation analysis occur a modular mode. Only formed trans interactions, supporting argument for putative specific role adhesion. Deletion mutants revealed two highly conserved regions as important protein crosstalk. particular, N-terminal half ectodomain was crucial interactions. By contrast, multimerization only partially dependent on domain but strongly C-terminal ectodomain. We further observed coexpression with or leads diminished generation Abeta42. current data suggest is due formation heteromeric complexes, opening way novel therapeutic strategies targeting these complexes.