Subcellular localization and dimerization of APLP1 are strikingly different from APP and APLP2
| Autor: | Lisa-Marie Munter, Philipp Voigt, Karolina D. Bobowski, Daniela Kaden, Michael Schaefer, Gerd Multhaup |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Amyloid beta-Peptides
Nerve Tissue Proteins Receptors Cell Surface Cell Biology Biology Subcellular localization Peptide Fragments Cell Line Cell biology Protease Nexins Amyloid beta-Protein Precursor Crosstalk (biology) Förster resonance energy transfer Ectodomain Live cell imaging Humans APLP1 Protein Multimerization APLP2 Intracellular |
| Zdroj: | Journal of Cell Science. 122:368-377 |
| ISSN: | 1477-9137 0021-9533 |
| DOI: | 10.1242/jcs.034058 |
| Popis: | 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 cell surface, whereas APP and APLP2 are mostly found in intracellular compartments. Homo- and heterotypic cis interactions of APP family members could be detected by FRET and co-immunoprecipitation analysis and occur in a modular mode. Only APLP1 formed trans interactions, supporting the argument for a putative specific role of APLP1 in cell adhesion. Deletion mutants of APP family members revealed two highly conserved regions as important for the protein crosstalk. In particular, the N-terminal half of the ectodomain was crucial for APP and APLP2 interactions. By contrast, multimerization of APLP1 was only partially dependent on this domain but strongly on the C-terminal half of the ectodomain. We further observed that coexpression of APP with APLP1 or APLP2 leads to diminished generation of Aβ42. The current data suggest that this is due to the formation of heteromeric complexes, opening the way for novel therapeutic strategies targeting these complexes. |
| Databáze: | OpenAIRE |
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