Homo- and heterodimerization of APP family members promotes intercellular adhesion.
The amyloid precursor protein (APP) plays a central role in Alzheimer's disease, but its physiological function and that of its mammalian paralogs, the amyloid precursor-like proteins 1 and 2 (APLPs), is still poorly understood. APP has been proposed to form dimers, a process that could promote cell adhesion via trans-dimerization. We investigated the dimerization and cell adhesion properties of APP/APLPs and provide evidence that all three paralogs are capable of forming homo- and heterocomplexes. Moreover, we show that trans-interaction of APP family proteins promotes cell-cell adhesion in a homo- and heterotypic fashion and that endogenous APLP2 is required for cell-cell adhesion in mouse embryonic fibroblasts. We further demonstrate interaction of all the three APP family members in mouse brain, genetic interdependence, and molecular interaction of APP and APLPs in synaptically enriched membrane compartments. Together, our results provide evidence that homo- and heterocomplexes of APP/APLPs promote trans-cellular adhesion in vivo.
Soba
Peter
P
ZMBH, University of Heidelberg, Heidelberg, Germany. p.soba@zmbh.uni-heidelberg.de
Eggert
Simone
S
Wagner
Katja
K
Zentgraf
Hanswalter
H
Siehl
Katjuscha
K
Kreger
Sylvia
S
Löwer
Alexander
A
Langer
Andreas
A
Merdes
Gunter
G
Paro
Renato
R
Masters
Colin L
CL
Müller
Ulrike
U
Kins
Stefan
S
Beyreuther
Konrad
K
D016564:Amyloid beta-Protein Precursor / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002448:Cell Adhesion; D019281:Dimerization; D005347:Fibroblasts / Q000378:metabolism / Q000502:physiology; D006801:Humans; D051379:Mice; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D058255:Protease Nexins; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface / Q000378:metabolism*; D013570:Synaptic Membranes / Q000737:chemistry / Q000378:metabolism
C489697:APLP1 protein, human; C084104:APLP2 protein, human; C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor; D009419:Nerve Tissue Proteins; D058255:Protease Nexins; D011956:Receptors, Cell Surface