A Scaffold Protein JIP-1b Enhances Amyloid Precursor Protein Phosphorylation by JNK and Its Association with Kinesin Light Chain 1

Inomata, Hajime; Nakamura, Yoshitaka; Hayakawa, Akira; Takata, Hitoshi; Suzuki, Toshiharu; Miyazawa, Keiji; Kitamura, Naomi

doi:10.1074/jbc.m212160200

Cited by 142 publications

(136 citation statements)

References 38 publications

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“…2A) suggest that if such an effect exists, it is of minor importance when compared with the indirect effect that involved cargo binding to kinesin-1. Cargo binding on the KLC subunits is thought to unfold and activate kinesin-1, allowing it to be recruited and walk on microtubules (25,33,34). We further demonstrated that the majority of microtubule-bound kinesin-1 carries JNK (mainly JNK-2) and that kinesin-1 is necessary to allow basal kinase activation through phosphorylation.…”

Section: Discussionmentioning

confidence: 71%

Kinesin-1 Regulates Microtubule Dynamics via a c-Jun N-terminal Kinase-dependent Mechanism

Daire

Giustiniani

Leroy-Gori

et al. 2009

Journal of Biological Chemistry

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In the kinesin family, all the molecular motors that have been implicated in the regulation of microtubule dynamics have been shown to stimulate microtubule depolymerization. Here, we report that kinesin-1 (also known as conventional kinesin or KIF5B) stimulates microtubule elongation and rescues. We show that microtubule-associated kinesin-1 carries the c-Jun N-terminal kinase (JNK) to allow its activation and that microtubule elongation requires JNK activity throughout the microtubule life cycle. We also show that kinesin-1 and JNK promoted microtubule rescues to similar extents. Stimulation of microtubule rescues by the kinesin-1/JNK pathway could not be accounted for by the rescue factor CLIP-170. Indeed only a dual inhibition of kinesin-1/JNK and CLIP-170 completely blocked rescues and led to extensive microtubule loss. We propose that the kinesin-1/JNK signaling pathway is a major regulator of microtubule dynamics in living cells and that it is required with the rescue factor CLIP-170 to allow cells to build their interphase microtubule network.

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Section: Discussionmentioning

confidence: 71%

Kinesin-1 Regulates Microtubule Dynamics via a c-Jun N-terminal Kinase-dependent Mechanism

Daire

Giustiniani

Leroy-Gori

et al. 2009

Journal of Biological Chemistry

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“…Reports of a direct interaction between APP and KLC1 (9), combined with genetic and other evidence (20,28,29,46), led to the hypothesis that APP can serve as a vesicle adaptor for kinesin-1 via its interaction with KLC1, and thus play a role in the recruitment of kinesin-1 to axonal vesicles. More recent evidence suggests that the attachment of APP to kinesin-1 may not be direct, but instead may require proteins of the c-Jun N-terminal kinase (JNK)-interacting proteins, specifically JIP-1/JIP-2 (26,27). In either case, the amount of APP is suggested to play a role in determining the amount of kinesin-1 on a vesicle and, therefore, the details of the movement behavior of that vesicle.…”

Section: Discussionmentioning

confidence: 99%

“…Previous work raised the possibility that APP could bind to KLC and thus kinesin-1 either directly or indirectly via complex formation with JIP1 (9,26,27), a proposal that has remained controversial in the field. Here, we set out to test a key in vivo prediction of the hypothesis that APP recruits kinesin-1 to vesicles by developing and implementing a rigorous method for high-throughput, subpixel colocalization of diffraction limited fluorescent puncta in 2D immunofluorescence images at a separation below the Rayleigh limit, i.e., with superresolution.…”

mentioning

confidence: 99%

Subpixel colocalization reveals amyloid precursor protein-dependent kinesin-1 and dynein association with axonal vesicles

Szpankowski

Encalada

Goldstein

2012

Proc. Natl. Acad. Sci. U.S.A.

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Intracellular transport of vesicles and organelles along microtubules is powered by kinesin and cytoplasmic dynein molecular motors. Both motors can attach to the same cargo and thus must be coordinated to ensure proper distribution of intracellular materials. Although a number of hypotheses have been proposed to explain how these motors are coordinated, considerable uncertainty remains, in part because of the absence of methods for assessing motor subunit composition on individual vesicular cargos. We developed a robust quantitative immunofluorescence method based on subpixel colocalization to elucidate relative kinesin-1 and cytoplasmic dynein motor subunit composition of individual, endogenous amyloid precursor protein (APP) vesicles in mouse hippocampal cells. The resulting method and data allow us to test a key in vivo prediction of the hypothesis that APP can recruit kinesin-1 to APP vesicles in neuronal axons. We found that APP levels are well-correlated with the amount of the light chain of kinesin-1 (KLC1) and the heavy chain of cytoplasmic dynein (DHC1) on vesicles. In addition, genetic reduction of APP diminishes KLC1 and DHC1 levels on APP cargos. Finally, our data reveal that reduction of KLC1 leads to decreased levels of DHC1 on APP vesicles, suggesting that KLC1 is necessary for the association of DHC1 to these cargos, and help to explain previously reported retrograde transport defects generated when kinesin-1 is reduced.axonal transport | microtubule motor recruitment | Alzheimer's disease M icrotubule-based transport of vesicles and organelles in neurons is coordinated by kinesin (anterograde) and cytoplasmic dynein (retrograde) motor complexes. These motor proteins and their regulators play critical roles in long-distance signaling events in neurons, neuronal regeneration, and in the development of neurodegenerative disease (1-3). Several diseases in humans, such as hereditary spastic paraplegia (4), CharcotMarie-Tooth type 2 (5), and ALS-like motor degeneration (6), have been linked directly to mutations in genes encoding motor proteins. Additionally, disruption of transport is thought to be an early and perhaps causative event in Alzheimer's disease, Parkinson disease, and ALS, where axonal pathologies including abnormal accumulations of proteins and organelles have been routinely observed (1).Kinesin-1 is composed of heavy chain (KHC or KIF5) and light chain (KLC) subunits (7,8). Motor activity is executed by KHC, and cargo binding and regulatory activities are carried out by both KHC and KLC (9-11). Dynein is a large protein complex with six subunits: a large dynein heavy chain (DHC), an intermediate and light-intermediate chain (DIC and DLIC), and three dynein light chains (DLC) (12). Several types of vesicles, including amyloid precursor protein (APP) vesicles, depend upon kinesin-1 (9, 13-17) for their anterograde movement in axons. These studies raised the possibility that APP transport and its influence on APP proteolytic processing play an important role in the development of Alzheim...

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“…Paxillin, a microtubule-associated scaffold protein, was shown to be phosphorylated as the result of the both the phospholipase C␥ 3JNK1 (16) and PI3K3ERK2 pathways (23). A functional connection between kinesin, a microtubule plus-end directed motor, and JNK activity has been reported (24). Moreover, dynein has been shown to be involved in MTOC polarization (25).…”

Section: Discussionmentioning

confidence: 99%

Many NK cell receptors activate ERK2 and JNK1 to trigger microtubule organizing center and granule polarization and cytotoxicity

Chen

Trivedi

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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A Scaffold Protein JIP-1b Enhances Amyloid Precursor Protein Phosphorylation by JNK and Its Association with Kinesin Light Chain 1

Cited by 142 publications

References 38 publications

Kinesin-1 Regulates Microtubule Dynamics via a c-Jun N-terminal Kinase-dependent Mechanism

Kinesin-1 Regulates Microtubule Dynamics via a c-Jun N-terminal Kinase-dependent Mechanism

Subpixel colocalization reveals amyloid precursor protein-dependent kinesin-1 and dynein association with axonal vesicles

Many NK cell receptors activate ERK2 and JNK1 to trigger microtubule organizing center and granule polarization and cytotoxicity

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