TY  - JOUR
A1  - Mayer, Magnus C.
A1  - Schauenburg, Linda
A1  - Thompson-Steckel, Greta
A1  - Dunsing, Valentin
A1  - Kaden, Daniela
A1  - Voigt, Philipp
A1  - Schaefer, Michael
A1  - Chiantia, Salvatore
A1  - Kennedy, Timothy E.
A1  - Multhaup, Gerhard
T1  - Amyloid precursor-like protein 1 (APLP1) exhibits stronger
zinc-dependent neuronal adhesion than amyloid precursor protein and
APLP2
JF  - Journal of neurochemistry
N2  - The amyloid precursor protein (APP) and its paralogs, amyloid precursor-like protein 1 (APLP1) and APLP2, are metalloproteins with a putative role both in synaptogenesis and in maintaining synapse structure. Here, we studied the effect of zinc on membrane localization, adhesion, and secretase cleavage of APP, APLP1, and APLP2 in cell culture and rat neurons. For this, we employed live-cell microscopy techniques, a microcontact printing adhesion assay and ELISA for protein detection in cell culture supernatants. We report that zinc induces the multimerization of proteins of the amyloid precursor protein family and enriches them at cellular adhesion sites. Thus, zinc facilitates the formation of de novo APP and APLP1 containing adhesion complexes, whereas it does not have such influence on APLP2. Furthermore, zinc-binding prevented cleavage of APP and APLPs by extracellular secretases. In conclusion, the complexation of zinc modulates neuronal functions of APP and APLPs by (i) regulating formation of adhesion complexes, most prominently for APLP1, and (ii) by reducing the concentrations of neurotrophic soluble APP/APLP ectodomains.
KW  - amyloid precursor protein
KW  - amyloid precursor-like protein
KW  - neuronal adhesion
KW  - number and brightness
KW  - zinc
Y1  - 2016
U6  - https://doi.org/10.1111/jnc.13540
SN  - 0022-3042
SN  - 1471-4159
VL  - 137
SP  - 266
EP  - 276
PB  - Wiley-Blackwell
CY  - Hoboken
ER  -