TY - JOUR
T1 - Quantitative analysis of APP axonal transport in neurons
T2 - Role of JIP1 in enhanced APP anterograde transport
AU - Chiba, Kyoko
AU - Araseki, Masahiko
AU - Nozawa, Keisuke
AU - Furukori, Keiko
AU - Araki, Yoichi
AU - Matsushima, Takahide
AU - Nakaya, Tadashi
AU - Hata, Saori
AU - Saito, Yuhki
AU - Uchida, Seiichi
AU - Okada, Yasushi
AU - Nairn, Angus C.
AU - Davis, Roger J.
AU - Yamamoto, Tohru
AU - Kinjo, Masataka
AU - Taru, Hidenori
AU - Suzuki, Toshiharu
N1 - Publisher Copyright:
© 2014 Chiba, Araseki, Nozawa, et al.
PY - 2014/11/5
Y1 - 2014/11/5
N2 - Alzheimer's β-amyloid precursor protein (APP) associates with kinesin-1 via JNK-interacting protein 1 (JIP1); however, the role of JIP1 in APP transport by kinesin-1 in neurons remains unclear. We performed a quantitative analysis to understand the role of JIP1 in APP axonal transport. In JIP1-deficient neurons, we find that both the fast velocity (∼2.7 μm/s) and high frequency (66%) of anterograde transport of APP cargo are impaired to a reduced velocity (∼1.83 μm/s) and a lower frequency (45%). We identified two novel elements linked to JIP1 function, located in the central region of JIP1b, that interact with the coiled-coil domain of kinesin light chain 1 (KLC1), in addition to the conventional interaction of the JIP1b 11-amino acid C-terminal (C11) region with the tetratricopeptide repeat of KLC1. High frequency of APP anterograde transport is dependent on one of the novel elements in JIP1b. Fast velocity of APP cargo transport requires the C11 domain, which is regulated by the second novel region of JIP1b. Furthermore, efficient APP axonal transport is not influenced by phosphorylation of APP at Thr-668, a site known to be phosphorylated by JNK. Our quantitative analysis indicates that enhanced fast-velocity and efficient high-frequency APP anterograde transport observed in neurons are mediated by novel roles of JIP1b.
AB - Alzheimer's β-amyloid precursor protein (APP) associates with kinesin-1 via JNK-interacting protein 1 (JIP1); however, the role of JIP1 in APP transport by kinesin-1 in neurons remains unclear. We performed a quantitative analysis to understand the role of JIP1 in APP axonal transport. In JIP1-deficient neurons, we find that both the fast velocity (∼2.7 μm/s) and high frequency (66%) of anterograde transport of APP cargo are impaired to a reduced velocity (∼1.83 μm/s) and a lower frequency (45%). We identified two novel elements linked to JIP1 function, located in the central region of JIP1b, that interact with the coiled-coil domain of kinesin light chain 1 (KLC1), in addition to the conventional interaction of the JIP1b 11-amino acid C-terminal (C11) region with the tetratricopeptide repeat of KLC1. High frequency of APP anterograde transport is dependent on one of the novel elements in JIP1b. Fast velocity of APP cargo transport requires the C11 domain, which is regulated by the second novel region of JIP1b. Furthermore, efficient APP axonal transport is not influenced by phosphorylation of APP at Thr-668, a site known to be phosphorylated by JNK. Our quantitative analysis indicates that enhanced fast-velocity and efficient high-frequency APP anterograde transport observed in neurons are mediated by novel roles of JIP1b.
UR - http://www.scopus.com/inward/record.url?scp=84908565117&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84908565117&partnerID=8YFLogxK
U2 - 10.1091/mbc.E14-06-1111
DO - 10.1091/mbc.E14-06-1111
M3 - Article
C2 - 25165140
AN - SCOPUS:84908565117
SN - 1059-1524
VL - 25
SP - 3569
EP - 3580
JO - Molecular biology of the cell
JF - Molecular biology of the cell
IS - 22
ER -