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Quantitative analysis of APP axonal transport in neurons: role of JIP1 in enhanced APP anterograde transport.

Chiba K, Araseki M, Nozawa K, Furukori K, Araki Y, Matsushima T, Nakaya T, Hata S, Saito Y, Uchida S, Okada Y, Nairn AC, Davis RJ, Yamamoto T, Kinjo M, Taru H, Suzuki T - Mol. Biol. Cell (2014)

Bottom Line: 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%).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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Neuroscience, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.

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Summary of binding between JIP1b and KLC1, and schematic interactions between APP, JIP1b, and KLC. (A) Structures of JIP1b used in this study. Numbers represent amino acid positions. The asterisk indicates the position of alanine substitution for tyrosine (Y705A). Summary of JIP1b interactions with KLC1 (FL), KLC1 TPR domains (TPR), and the KLC1 N200 region (N200) is shown on the right, classified as binding (+), weak binding (±), and nonbinding (–). N.D., not determined. (B) Schematic interaction between the APP cytoplasmic region, JIP1b, and KLC. The NPTY motif of APP binds to the PI/PTB domain of JIP1b. Thr-668 in APP (numbering for APP695 isoform) is subject to phosphorylation. The 11 C-terminal amino acids of JIP (697YTCPTEDIYLE707), including Tyr-705, interact with the C-terminal half of KLC1, including the TPR motifs. The JIP1b370-402 and JIP1b465-483 regions were identified as novel binding sites for the N-terminal half of KLC1, including the coiled-coil/heptad repeats. The JIP1b465-483 region also showed regulatory activity in the interaction between the 11 C-terminal amino acids of JIP1b and the C-terminal half of KLC1. The C11-terminal region of JIP1b may be involved in the interaction between JIP1b465-483 and the N-terminal half of KLC1.
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Figure 4: Summary of binding between JIP1b and KLC1, and schematic interactions between APP, JIP1b, and KLC. (A) Structures of JIP1b used in this study. Numbers represent amino acid positions. The asterisk indicates the position of alanine substitution for tyrosine (Y705A). Summary of JIP1b interactions with KLC1 (FL), KLC1 TPR domains (TPR), and the KLC1 N200 region (N200) is shown on the right, classified as binding (+), weak binding (±), and nonbinding (–). N.D., not determined. (B) Schematic interaction between the APP cytoplasmic region, JIP1b, and KLC. The NPTY motif of APP binds to the PI/PTB domain of JIP1b. Thr-668 in APP (numbering for APP695 isoform) is subject to phosphorylation. The 11 C-terminal amino acids of JIP (697YTCPTEDIYLE707), including Tyr-705, interact with the C-terminal half of KLC1, including the TPR motifs. The JIP1b370-402 and JIP1b465-483 regions were identified as novel binding sites for the N-terminal half of KLC1, including the coiled-coil/heptad repeats. The JIP1b465-483 region also showed regulatory activity in the interaction between the 11 C-terminal amino acids of JIP1b and the C-terminal half of KLC1. The C11-terminal region of JIP1b may be involved in the interaction between JIP1b465-483 and the N-terminal half of KLC1.

Mentions: The various JIP1b mutants used in this study. and their ability to bind to different regions of KLC1 are summarized in Figure 4A. In addition to the known interaction between JIP1b C11 and TPR motifs of KLC1, two novel interactions were found: binding of the 370–402 and 465–483 regions of JIP1b to the N-terminal region of KLC1, which forms a coiled-coil structure. Furthermore, the 465–483 region of JIP1b plays an important role in regulating the association between JIP1b C11 and TPR motifs of KLC1, or possibly in preserving the physiological conformation of JIP1b, to interact with KLC1. A schematic of the interaction between JIP1b and KLC and its regulation is shown in Figure 4B.


Quantitative analysis of APP axonal transport in neurons: role of JIP1 in enhanced APP anterograde transport.

Chiba K, Araseki M, Nozawa K, Furukori K, Araki Y, Matsushima T, Nakaya T, Hata S, Saito Y, Uchida S, Okada Y, Nairn AC, Davis RJ, Yamamoto T, Kinjo M, Taru H, Suzuki T - Mol. Biol. Cell (2014)

Summary of binding between JIP1b and KLC1, and schematic interactions between APP, JIP1b, and KLC. (A) Structures of JIP1b used in this study. Numbers represent amino acid positions. The asterisk indicates the position of alanine substitution for tyrosine (Y705A). Summary of JIP1b interactions with KLC1 (FL), KLC1 TPR domains (TPR), and the KLC1 N200 region (N200) is shown on the right, classified as binding (+), weak binding (±), and nonbinding (–). N.D., not determined. (B) Schematic interaction between the APP cytoplasmic region, JIP1b, and KLC. The NPTY motif of APP binds to the PI/PTB domain of JIP1b. Thr-668 in APP (numbering for APP695 isoform) is subject to phosphorylation. The 11 C-terminal amino acids of JIP (697YTCPTEDIYLE707), including Tyr-705, interact with the C-terminal half of KLC1, including the TPR motifs. The JIP1b370-402 and JIP1b465-483 regions were identified as novel binding sites for the N-terminal half of KLC1, including the coiled-coil/heptad repeats. The JIP1b465-483 region also showed regulatory activity in the interaction between the 11 C-terminal amino acids of JIP1b and the C-terminal half of KLC1. The C11-terminal region of JIP1b may be involved in the interaction between JIP1b465-483 and the N-terminal half of KLC1.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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Figure 4: Summary of binding between JIP1b and KLC1, and schematic interactions between APP, JIP1b, and KLC. (A) Structures of JIP1b used in this study. Numbers represent amino acid positions. The asterisk indicates the position of alanine substitution for tyrosine (Y705A). Summary of JIP1b interactions with KLC1 (FL), KLC1 TPR domains (TPR), and the KLC1 N200 region (N200) is shown on the right, classified as binding (+), weak binding (±), and nonbinding (–). N.D., not determined. (B) Schematic interaction between the APP cytoplasmic region, JIP1b, and KLC. The NPTY motif of APP binds to the PI/PTB domain of JIP1b. Thr-668 in APP (numbering for APP695 isoform) is subject to phosphorylation. The 11 C-terminal amino acids of JIP (697YTCPTEDIYLE707), including Tyr-705, interact with the C-terminal half of KLC1, including the TPR motifs. The JIP1b370-402 and JIP1b465-483 regions were identified as novel binding sites for the N-terminal half of KLC1, including the coiled-coil/heptad repeats. The JIP1b465-483 region also showed regulatory activity in the interaction between the 11 C-terminal amino acids of JIP1b and the C-terminal half of KLC1. The C11-terminal region of JIP1b may be involved in the interaction between JIP1b465-483 and the N-terminal half of KLC1.
Mentions: The various JIP1b mutants used in this study. and their ability to bind to different regions of KLC1 are summarized in Figure 4A. In addition to the known interaction between JIP1b C11 and TPR motifs of KLC1, two novel interactions were found: binding of the 370–402 and 465–483 regions of JIP1b to the N-terminal region of KLC1, which forms a coiled-coil structure. Furthermore, the 465–483 region of JIP1b plays an important role in regulating the association between JIP1b C11 and TPR motifs of KLC1, or possibly in preserving the physiological conformation of JIP1b, to interact with KLC1. A schematic of the interaction between JIP1b and KLC and its regulation is shown in Figure 4B.

Bottom Line: 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%).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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Neuroscience, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.

Show MeSH