Kinesin‐2 differentially regulates the anterograde axonal transports of acetylcholinesterase and choline acetyltransferase in <i>Drosophila</i>

Baqri, Rehan M.; Charan, Rakshita A.; Schimmelpfeng, Kristina; Chavan, Swati; Ray, Krishanu

doi:10.1002/neu.20230

Cited by 23 publications

(31 citation statements)

References 52 publications

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“…These observations suggested that, unlike the kinesin‐1 mutants , the axon channels were not blocked in the Klp64D mutant. Together with the previous data , these results established that ChAT transport by kinesin‐2 in the axons requires an interaction with the KLP64D tail.…”

Section: Resultssupporting

confidence: 84%

Interaction with a Kinesin‐2 Tail Propels Choline Acetyltransferase Flow Towards Synapse

Sadananda

Hamid

Doodhi

et al. 2012

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Bulk flow constitutes a substantial part of the slow transport of soluble proteins in axons. Though the underlying mechanism is unclear, evidences indicate that intermittent, kinesin based movement of large protein-aggregates aids this process. Choline acetyl-transferase (ChAT), a soluble enzyme catalyzing acetylcholine synthesis, propagates towards synapse at an intermediate, slow rate. The presynaptic enrichment of ChAT requires heterotrimeric kinesin-2, comprising KLP64D, KLP68D and DmKAP, in Drosophila. Here, we show that the bulk flow of a recombinant Green Fluorescent Protein-tagged ChAT (GFP::ChAT), in Drosophila axons, lacks particulate features. It occurs for a brief period during the larval stages. In addition, both the endogenous ChAT and GFP::ChAT directly bind to the KLP64D tail, which is essential for the GFP::ChAT entry and anterograde flow in axon. These evidences suggest that a direct interaction with motor proteins could regulate the bulk flow of soluble proteins, and thus establish their asymmetric distribution.

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Section: Resultssupporting

confidence: 84%

Interaction with a Kinesin‐2 Tail Propels Choline Acetyltransferase Flow Towards Synapse

Sadananda

Hamid

Doodhi

et al. 2012

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“…Phosphorylated cJun N-terminal Kinase (p-JNK) localization was found throughout the neuron (Figure S4E), complementary to larval nerves (Figure S5ABC) [53]. An antibody against Choline Acetyltransferase (ChAT), a cholinergic neuron marker, was localized in high concentrations to the cell body and minimally in projections and growth cones (Figure S4F), similar to what was previously observed in whole mount larvae [54]–[56] (Figure S5ABC). Highwire, a negative regulator of NMJ growth [57]–[59], localized to neuronal cell bodies and growth cones, and minimal localization was seen within projections (Figure S4G).…”

Section: Resultssupporting

confidence: 78%

Spatial and Temporal Characteristics of Normal and Perturbed Vesicle Transport

et al. 2014

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Efficient intracellular transport is essential for healthy cellular function and structural integrity, and problems in this pathway can lead to neuronal cell death and disease. To spatially and temporally evaluate how transport defects are initiated, we adapted a primary neuronal culture system from Drosophila larval brains to visualize the movement dynamics of several cargos/organelles along a 90 micron axonal neurite over time. All six vesicles/organelles imaged showed robust bi-directional motility at both day 1 and day 2. Reduction of motor proteins decreased the movement of vesicles/organelles with increased numbers of neurite blocks. Neuronal growth was also perturbed with reduction of motor proteins. Strikingly, we found that all blockages were not fixed, permanent blocks that impeded transport of vesicles as previously thought, but that some blocks were dynamic clusters of vesicles that resolved over time. Taken together, our findings suggest that non-resolving blocks may likely initiate deleterious pathways leading to death and degeneration, while resolving blocks may be benign. Therefore evaluating the spatial and temporal characteristics of vesicle transport has important implications for our understanding of how transport defects can affect other pathways to initiate death and degeneration.

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“…To test this possibility, we examined their localizations in tissues. Both an available anti-Klp64D antibody (Baqri et al, 2006) and our newly generated antibodies specifically detected Klp64D protein on a western blot, but could not recognize the protein in tissues by immunocytochemical staining. Thus, we generated a transgenic fly line that carries UAS-Klp64D-HA (Hemagglutinin).…”

Section: Klp64d Shows Overlapping Subcellular Localization With Arm Amentioning

confidence: 94%

Kinesin-II recruits Armadillo and Dishevelled for Wingless signaling in Drosophila

Vuong

Mukhopadhyay²,

Choi

2014

Development

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Wingless (Wg)/Wnt signaling is fundamental in metazoan development. Armadillo (Arm)/β-catenin and Dishevelled (Dsh) are key components of Wnt signal transduction. Recent studies suggest that intracellular trafficking of Wnt signaling components is important, but underlying mechanisms are not well known. Here, we show that Klp64D, the Drosophila homolog of Kif3A kinesin II subunit, is required for Wg signaling by regulating Arm during wing development. Mutations in klp64D or RNAi cause wing notching and loss of Wg target gene expression. The wing notching phenotype by Klp64D knockdown is suppressed by activated Arm but not by Dsh, suggesting that Klp64D is required for Arm function. Furthermore, klp64D and arm mutants show synergistic genetic interaction. Consistent with this genetic interaction, Klp64D directly binds to the Arm repeat domain of Arm and can recruit Dsh in the presence of Arm. Overexpression of Klp64D mutated in the motor domain causes dominant wing notching, indicating the importance of the motor activity. Klp64D shows subcellular localization to intracellular vesicles overlapping with Arm and Dsh. In klp64D mutants, Arm is abnormally accumulated in vesicular structures including Golgi, suggesting that intracellular trafficking of Arm is affected. Human KIF3A can also bind β-catenin and rescue klp64D RNAi phenotypes. Taken together, we propose that Klp64D is essential for Wg signaling by trafficking of Arm via the formation of a conserved complex with Arm.

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Kinesin‐2 differentially regulates the anterograde axonal transports of acetylcholinesterase and choline acetyltransferase in Drosophila

Cited by 23 publications

References 52 publications

Interaction with a Kinesin‐2 Tail Propels Choline Acetyltransferase Flow Towards Synapse

Interaction with a Kinesin‐2 Tail Propels Choline Acetyltransferase Flow Towards Synapse

Spatial and Temporal Characteristics of Normal and Perturbed Vesicle Transport

Kinesin-II recruits Armadillo and Dishevelled for Wingless signaling in Drosophila

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