TY - JOUR
T1 - Amyloid β protein precursor (AβPP), but not AβPP-like protein 2, is bridged to the kinesin light chain by the scaffold protein JNK-interacting protein 1
AU - Matsuda, Shuji
AU - Matsuda, Yukiko
AU - D'Adamio, Luciano
PY - 2003/10/3
Y1 - 2003/10/3
N2 - Proteolytic processing of amyloid β protein precursor (AβPP) generates peptides that regulate normal cell signaling and are implicated in Alzheimer's disease pathogenesis. AβPP processing also occurs in nerve processes where AβPP is transported from the cell body by kinesin-I, a microtubule motor composed of two kinesin heavy chain and two kinesin light chain (Klc) subunits. AβPP transport is supposedly mediated by the direct AβPP-Klc1 interaction. Here we demonstrate that the AβPP-Klc1 interaction is not direct but is mediated by JNK-interacting protein J (JIP1). The phosphotyrosine binding domain of JIP1 binds the cytoplasmic tail of AβPP, whereas the JIP1 C-terminal region interacts with the tetratrico-peptide repeats of Klc1. We also show that JIP1 does not bridge the AβPP gene family member AβPP-like protein 2, APLP2, to Klc1. These results support a model where JIP1 mediates the interaction of AβPP to the motor protein kinesin-I and that this JIP1 function is unique for AβPP relative to its family member APLP2. Our data suggest that kinesin-II-dependent neuronal AβPP transport, which controls AβPP processing, may be regulated by JIP1.
AB - Proteolytic processing of amyloid β protein precursor (AβPP) generates peptides that regulate normal cell signaling and are implicated in Alzheimer's disease pathogenesis. AβPP processing also occurs in nerve processes where AβPP is transported from the cell body by kinesin-I, a microtubule motor composed of two kinesin heavy chain and two kinesin light chain (Klc) subunits. AβPP transport is supposedly mediated by the direct AβPP-Klc1 interaction. Here we demonstrate that the AβPP-Klc1 interaction is not direct but is mediated by JNK-interacting protein J (JIP1). The phosphotyrosine binding domain of JIP1 binds the cytoplasmic tail of AβPP, whereas the JIP1 C-terminal region interacts with the tetratrico-peptide repeats of Klc1. We also show that JIP1 does not bridge the AβPP gene family member AβPP-like protein 2, APLP2, to Klc1. These results support a model where JIP1 mediates the interaction of AβPP to the motor protein kinesin-I and that this JIP1 function is unique for AβPP relative to its family member APLP2. Our data suggest that kinesin-II-dependent neuronal AβPP transport, which controls AβPP processing, may be regulated by JIP1.
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U2 - 10.1074/jbc.M304379200
DO - 10.1074/jbc.M304379200
M3 - Article
C2 - 12893827
AN - SCOPUS:0141532147
SN - 0021-9258
VL - 278
SP - 38601
EP - 38606
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 40
ER -