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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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Related in: MedlinePlus

Functional interaction between APP, JIP1b, and KLC of kinesin-1. Possible regulation of APP cargo transport by protein interactions is shown schematically. 1) Association of JIP1b C11 to the TPR motif of KLC1 is required for the enhanced fast velocity of anterograde transport of APP cargo. 2) Interaction of JIP1b465-483 with KLC1 N200 regulates the association of JIP1b C11 to the TPR motif of KLC1 and is thus essential for the enhanced fast velocity of anterograde transport of APP cargo. This interaction may also be involved in the decrease of the stationary APP cargo. 3) Interaction of JIP1b370-402 with KLC1 N200 contributes to the stable and higher-frequency anterograde transport of APP cargo. 4) Interaction of the JIP1b PI/PTB domain with the APP cytoplasmic NPTY motif is essential for the enhanced fast velocity and higher frequency of anterograde transport of APP cargo. 5) Interaction of JIP1b JBD with JNK is not involved in the enhanced fast velocity of anterograde transport of APP cargo. 6) Phosphorylation of APP at cytoplasmic Thr668 is not involved in the efficient APP anterograde transport by kinesin-1. 7) APP cargoes may interact with kinesin-1 independently of JIP1 to be transported anterogradely with slower velocity. An unknown factor, X, may mediate the interaction of APP with kinesin-1, or APP can directly associate with kinesin-1 in the absence of JIP1.
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Figure 6: Functional interaction between APP, JIP1b, and KLC of kinesin-1. Possible regulation of APP cargo transport by protein interactions is shown schematically. 1) Association of JIP1b C11 to the TPR motif of KLC1 is required for the enhanced fast velocity of anterograde transport of APP cargo. 2) Interaction of JIP1b465-483 with KLC1 N200 regulates the association of JIP1b C11 to the TPR motif of KLC1 and is thus essential for the enhanced fast velocity of anterograde transport of APP cargo. This interaction may also be involved in the decrease of the stationary APP cargo. 3) Interaction of JIP1b370-402 with KLC1 N200 contributes to the stable and higher-frequency anterograde transport of APP cargo. 4) Interaction of the JIP1b PI/PTB domain with the APP cytoplasmic NPTY motif is essential for the enhanced fast velocity and higher frequency of anterograde transport of APP cargo. 5) Interaction of JIP1b JBD with JNK is not involved in the enhanced fast velocity of anterograde transport of APP cargo. 6) Phosphorylation of APP at cytoplasmic Thr668 is not involved in the efficient APP anterograde transport by kinesin-1. 7) APP cargoes may interact with kinesin-1 independently of JIP1 to be transported anterogradely with slower velocity. An unknown factor, X, may mediate the interaction of APP with kinesin-1, or APP can directly associate with kinesin-1 in the absence of JIP1.

Mentions: Our observations indicate that 1) the interaction between the TPR motifs of KLC1 and the C11 region, including Tyr-705 of JIP1b, is essential for the enhanced fast anterograde transport of APP cargo; 2) a novel element within amino acids 370–402 of JIP1b is required for preservation and/or stabilization of the higher frequency of APP anterograde transport through interaction with the N-terminal region of KLC1; 3) another novel element, amino acids 465–483 of JIP1b, regulates the interaction of the KLC1 TPR domain with the JIP1b C11 domain through an association with the N-terminal region of KLC1; 4) this interaction may also contribute to APP cargo stabilization and/or activation of anterograde transport; and 5) phosphorylation of APP at Thr-668 does not contribute to the increased efficiency of APP cargo transport. The functional interactions among APP, JIP1b, and KLC of kinesin-1 are illustrated in Figure 6.


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)

Functional interaction between APP, JIP1b, and KLC of kinesin-1. Possible regulation of APP cargo transport by protein interactions is shown schematically. 1) Association of JIP1b C11 to the TPR motif of KLC1 is required for the enhanced fast velocity of anterograde transport of APP cargo. 2) Interaction of JIP1b465-483 with KLC1 N200 regulates the association of JIP1b C11 to the TPR motif of KLC1 and is thus essential for the enhanced fast velocity of anterograde transport of APP cargo. This interaction may also be involved in the decrease of the stationary APP cargo. 3) Interaction of JIP1b370-402 with KLC1 N200 contributes to the stable and higher-frequency anterograde transport of APP cargo. 4) Interaction of the JIP1b PI/PTB domain with the APP cytoplasmic NPTY motif is essential for the enhanced fast velocity and higher frequency of anterograde transport of APP cargo. 5) Interaction of JIP1b JBD with JNK is not involved in the enhanced fast velocity of anterograde transport of APP cargo. 6) Phosphorylation of APP at cytoplasmic Thr668 is not involved in the efficient APP anterograde transport by kinesin-1. 7) APP cargoes may interact with kinesin-1 independently of JIP1 to be transported anterogradely with slower velocity. An unknown factor, X, may mediate the interaction of APP with kinesin-1, or APP can directly associate with kinesin-1 in the absence of JIP1.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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Figure 6: Functional interaction between APP, JIP1b, and KLC of kinesin-1. Possible regulation of APP cargo transport by protein interactions is shown schematically. 1) Association of JIP1b C11 to the TPR motif of KLC1 is required for the enhanced fast velocity of anterograde transport of APP cargo. 2) Interaction of JIP1b465-483 with KLC1 N200 regulates the association of JIP1b C11 to the TPR motif of KLC1 and is thus essential for the enhanced fast velocity of anterograde transport of APP cargo. This interaction may also be involved in the decrease of the stationary APP cargo. 3) Interaction of JIP1b370-402 with KLC1 N200 contributes to the stable and higher-frequency anterograde transport of APP cargo. 4) Interaction of the JIP1b PI/PTB domain with the APP cytoplasmic NPTY motif is essential for the enhanced fast velocity and higher frequency of anterograde transport of APP cargo. 5) Interaction of JIP1b JBD with JNK is not involved in the enhanced fast velocity of anterograde transport of APP cargo. 6) Phosphorylation of APP at cytoplasmic Thr668 is not involved in the efficient APP anterograde transport by kinesin-1. 7) APP cargoes may interact with kinesin-1 independently of JIP1 to be transported anterogradely with slower velocity. An unknown factor, X, may mediate the interaction of APP with kinesin-1, or APP can directly associate with kinesin-1 in the absence of JIP1.
Mentions: Our observations indicate that 1) the interaction between the TPR motifs of KLC1 and the C11 region, including Tyr-705 of JIP1b, is essential for the enhanced fast anterograde transport of APP cargo; 2) a novel element within amino acids 370–402 of JIP1b is required for preservation and/or stabilization of the higher frequency of APP anterograde transport through interaction with the N-terminal region of KLC1; 3) another novel element, amino acids 465–483 of JIP1b, regulates the interaction of the KLC1 TPR domain with the JIP1b C11 domain through an association with the N-terminal region of KLC1; 4) this interaction may also contribute to APP cargo stabilization and/or activation of anterograde transport; and 5) phosphorylation of APP at Thr-668 does not contribute to the increased efficiency of APP cargo transport. The functional interactions among APP, JIP1b, and KLC of kinesin-1 are illustrated in Figure 6.

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
Related in: MedlinePlus