The Experts below are selected from a list of 13935864 Experts worldwide ranked by ideXlab platform
Nobutaka Hirokawa - One of the best experts on this subject based on the ideXlab platform.
-
KIF1Bβ mutations detected in hereditary neuropathy impair IGF1R transport and axon growth
The Journal of cell biology, 2018Co-Authors: Hironori Takahashi, Shinsuke Niwa, Yosuke Tanaka, Sotaro Ichinose, Matthew Wicklund, Nobutaka HirokawaAbstract:KIF1Bβ is a kinesin-3 family anterograde motor protein essential for neuronal development, viability, and function. KIF1Bβ mutations have previously been reported in a limited number of pedigrees of Charcot-Marie-Tooth disease type 2A (CMT2A) neuropathy. However, the gene responsible for CMT2A is still controversial, and the mechanism of pathogenesis remains elusive. In this study, we show that the receptor tyrosine kinase IGF1R is a new direct binding partner of KIF1Bβ, and its binding and transport is specifically impaired by the Y1087C mutation of KIF1Bβ, which we detected in hereditary neuropathic patients. The axonal outgrowth and IGF-I signaling of KIF1B-/- neurons were significantly impaired, consistent with decreased surface IGF1R expression. The complementary capacity of KIF1Bβ-Y1087C of these phenotypes was significantly impaired, but the binding capacity to synaptic vesicle precursors was not affected. These data have supported the relevance of KIF1Bβ in IGF1R transport, which may give new clue to the neuropathic pathogenesis.
-
the molecular motor kif1a transports the trka neurotrophin receptor and is essential for sensory neuron survival and function
Neuron, 2016Co-Authors: Yosuke Tanaka, Shinsuke Niwa, Atena Farkhondeh, Ruyun Zhou, Ming Dong, Nobutaka Hirokawa, Li WangAbstract:Summary KIF1A is a major axonal transport motor protein, but its functional significance remains elusive. Here we show that KIF1A-haploinsufficient mice developed sensory neuropathy. We found progressive loss of TrkA(+) sensory neurons in Kif1a +/− dorsal root ganglia (DRGs). Moreover, axonal transport of TrkA was significantly disrupted in Kif1a +/− neurons. Live imaging and immunoprecipitation assays revealed that KIF1A bound to TrkA-containing vesicles through the adaptor GTP-Rab3, suggesting that TrkA is a cargo of the KIF1A motor. Physiological measurements revealed a weaker capsaicin response in Kif1a +/− DRG neurons. Moreover, these neurons were hyposensitive to nerve growth factor, which could explain the reduced neuronal survival and the functional deficiency of the pain receptor TRPV1. Because phosphatidylinositol 3-kinase (PI3K) signaling significantly rescued these phenotypes and also increased Kif1a mRNA, we propose that KIF1A is essential for the survival and function of sensory neurons because of the TrkA transport and its synergistic support of the NGF/TrkA/PI3K signaling pathway.
-
Intracellular transport, molecular motors, KIFs and related diseases
BMC Genomics, 2014Co-Authors: Nobutaka HirokawaAbstract:The intracellular transport is fundamental for cellular functions, morphogenesis and survival in general including neurons composed of a very long axon and dendrites. We discovered most of the kinesin superfamily motor proteins, KIFs, 45 genes in mammals, elucidated their molecular structures and functional roles by molecular cell biology, molecular genetics, biophysics and structural biology and successfully disclosed the mechanism of intracellular transport fundamental for neuronal functions. In the axon and dendrites KIFs transport their cargos such as synaptic vesicle precursors (KIF1A/KIF1Bbeta), mitochondria (KIF1Balpha/KIF5s), plasma membrane proteins (KIF3/KIF5s), NMDA glutamate receptors (KIF17), AMPA receptors (KIF5s) and mRNA with large protein complex (KIF5s). KIFs mainly recognize and bind their cargoes through adaptor protein complex and release them via phosphorylation of KIFs or GTP hydrolyses of cargo G-protein. Furthermore, using molecular genetics we successfully uncovered that KIFs play significant roles for fundamental physiological phenomena in development and functions of nervous system and that deletion of KIFs causes certain diseases by clarifying followings: 1) KIF1A/KIF1B beta hetero mice serve as a model for neuropathy, 2) KIF3 determines left/right asymmetry by generating cilia and nodal flow in the node of early embryos, 3) KIF17 plays a fundamental role on learning and memory by not only transporting NMDA glutamate receptor in dendrites but also controlling transcription and translation of KIF17 and NMDA receptor mRNAs by enhancing phosphorylated CREB, 4) KIF1A is essential for hippocampal synaptogenesis and learning enhancement in an enriched environment, 5) KIF2A is fundamental for brain wiring by controlling unnecessary elongation of growth cones by depolymerizing microtubules, 6) KIF4 plays a crucial role in the activity-dependent survival of postmitotic neurons in brain development by regulating poly(ADP-ribose) polymerase-1 activity, 7) KIF26A is essential for enteric neuronal development by regulating GDNF-Ret signaling, 8) KIF3 suppresses tumorigenesis by transporting beta-catenin from Golgi to plasma membrane for serving as cell-cell adhesion molecules, inhibiting its accumulation in the nucleus and suppressing hyper proliferation of progenitor cells, 9)KIF5A is essential for GABAa receptor transport and KIF5A deletion causes epilepsy, 10)KIF19A is a microtubule depolymerizing KIF for ciliary length control and its deletion causes female infertility and hydrocephalus based on affected fluid flows, 11)KIF13A transports serotonin receptors to plasma membranes and its deletion causes elevated–anxiety phenotypes. Thus, KIFs play significant roles not only at cellular level, but also in brain function and development. Further, their malfunctions cause diseases such as neuropathy, epilepsy, dementia, elevated anxiety, tumor, megacolon and hydrocephalus.
-
Regulation of NMDA Receptor Transport: A KIF17–Cargo Binding/Releasing Underlies Synaptic Plasticity and Memory In Vivo
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012Co-Authors: Xiling Yin, Yosuke Takei, Xue Feng, Nobutaka HirokawaAbstract:Regulation of NMDA receptor trafficking is crucial to modulate neuronal communication. Ca 2+ /calmodulin-dependent protein kinase phosphorylates the tail domain of KIF17, a member of the kinesin superfamily, to control NMDA receptor subunit 2B (GluN2B) transport by changing the KIF17–cargo interaction in vitro . However, the mechanisms of regulation of GluN2B transport in vivo and its physiological significance are unknown. We generated transgenic mice carrying wild-type KIF17 ( TgS ), or KIF17 with S1029A ( TgA ) or S1029D ( TgD ) phosphomimic mutations in kif17 −/− background. TgA/kif17 −/− and TgD/kif17 −/− mice exhibited reductions in synaptic NMDA receptors because of their inability to load/unload GluN2B onto/from KIF17, leading to impaired neuronal plasticity, CREB activation, and spatial memory. Expression of GFP-KIF17 in TgS/kif17 −/− mouse neurons rescued the synaptic and behavioral defects of kif17 −/− mice. These results suggest that phosphorylation-based regulation of NMDA receptor transport is critical for learning and memory in vivo .
-
regulation of nmda receptor transport a kif17 cargo binding releasing underlies synaptic plasticity and memory in vivo
The Journal of Neuroscience, 2012Co-Authors: Xiling Yin, Yosuke Takei, Nobutaka Hirokawa, Xue FengAbstract:Regulation of NMDA receptor trafficking is crucial to modulate neuronal communication. Ca 2+ /calmodulin-dependent protein kinase phosphorylates the tail domain of KIF17, a member of the kinesin superfamily, to control NMDA receptor subunit 2B (GluN2B) transport by changing the KIF17–cargo interaction in vitro . However, the mechanisms of regulation of GluN2B transport in vivo and its physiological significance are unknown. We generated transgenic mice carrying wild-type KIF17 ( TgS ), or KIF17 with S1029A ( TgA ) or S1029D ( TgD ) phosphomimic mutations in kif17 −/− background. TgA/kif17 −/− and TgD/kif17 −/− mice exhibited reductions in synaptic NMDA receptors because of their inability to load/unload GluN2B onto/from KIF17, leading to impaired neuronal plasticity, CREB activation, and spatial memory. Expression of GFP-KIF17 in TgS/kif17 −/− mouse neurons rescued the synaptic and behavioral defects of kif17 −/− mice. These results suggest that phosphorylation-based regulation of NMDA receptor transport is critical for learning and memory in vivo .
Yosuke Takei - One of the best experts on this subject based on the ideXlab platform.
-
regulation of nmda receptor transport a kif17 cargo binding releasing underlies synaptic plasticity and memory in vivo
The Journal of Neuroscience, 2012Co-Authors: Xiling Yin, Yosuke Takei, Nobutaka Hirokawa, Xue FengAbstract:Regulation of NMDA receptor trafficking is crucial to modulate neuronal communication. Ca 2+ /calmodulin-dependent protein kinase phosphorylates the tail domain of KIF17, a member of the kinesin superfamily, to control NMDA receptor subunit 2B (GluN2B) transport by changing the KIF17–cargo interaction in vitro . However, the mechanisms of regulation of GluN2B transport in vivo and its physiological significance are unknown. We generated transgenic mice carrying wild-type KIF17 ( TgS ), or KIF17 with S1029A ( TgA ) or S1029D ( TgD ) phosphomimic mutations in kif17 −/− background. TgA/kif17 −/− and TgD/kif17 −/− mice exhibited reductions in synaptic NMDA receptors because of their inability to load/unload GluN2B onto/from KIF17, leading to impaired neuronal plasticity, CREB activation, and spatial memory. Expression of GFP-KIF17 in TgS/kif17 −/− mouse neurons rescued the synaptic and behavioral defects of kif17 −/− mice. These results suggest that phosphorylation-based regulation of NMDA receptor transport is critical for learning and memory in vivo .
-
Regulation of NMDA Receptor Transport: A KIF17–Cargo Binding/Releasing Underlies Synaptic Plasticity and Memory In Vivo
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012Co-Authors: Xiling Yin, Yosuke Takei, Xue Feng, Nobutaka HirokawaAbstract:Regulation of NMDA receptor trafficking is crucial to modulate neuronal communication. Ca 2+ /calmodulin-dependent protein kinase phosphorylates the tail domain of KIF17, a member of the kinesin superfamily, to control NMDA receptor subunit 2B (GluN2B) transport by changing the KIF17–cargo interaction in vitro . However, the mechanisms of regulation of GluN2B transport in vivo and its physiological significance are unknown. We generated transgenic mice carrying wild-type KIF17 ( TgS ), or KIF17 with S1029A ( TgA ) or S1029D ( TgD ) phosphomimic mutations in kif17 −/− background. TgA/kif17 −/− and TgD/kif17 −/− mice exhibited reductions in synaptic NMDA receptors because of their inability to load/unload GluN2B onto/from KIF17, leading to impaired neuronal plasticity, CREB activation, and spatial memory. Expression of GFP-KIF17 in TgS/kif17 −/− mouse neurons rescued the synaptic and behavioral defects of kif17 −/− mice. These results suggest that phosphorylation-based regulation of NMDA receptor transport is critical for learning and memory in vivo .
-
molecular motor kif17 is fundamental for memory and learning via differential support of synaptic nr2a 2b levels
Neuron, 2011Co-Authors: Yosuke Takei, Mizuho A Kido, Nobutaka HirokawaAbstract:Summary Kinesin superfamily motor protein 17 (KIF17) is a candidate transporter of N-methyl-D-aspartate (NMDA) receptor subunit 2B (NR2B). Disruption of the murine kif17 gene inhibits NR2B transport, accompanied by decreased transcription of nr2b , resulting in a loss of synaptic NR2B. In kif17 −/− hippocampal neurons, the NR2A level is also decreased because of accelerated ubiquitin-proteasome system-dependent degradation. Accordingly, NMDA receptor-mediated synaptic currents, early and late long-term potentiation, long-term depression, and CREB responses are attenuated in kif17 −/− neurons, concomitant with a hippocampus-dependent memory impairment in knockout mice. In wild-type neurons, CREB is activated by synaptic inputs, which increase the levels of KIF17 and NR2B. Thus, KIF17 differentially maintains the levels of NR2A and NR2B, and, when synapses are stimulated, the NR2B/KIF17 complex is upregulated on demand through CREB activity. These KIF17-based mechanisms for maintaining NR2A/2B levels could underlie multiple phases of memory processes in vivo.
-
charcot marie tooth disease type 2a caused by mutation in a microtubule motor KIF1Bβ
Cell, 2001Co-Authors: Chunjie Zhao, Junko Takita, Terunaga Nakagawa, Sen Takeda, Takao Nakata, Sumio Terada, Yosuke Tanaka, Hongwei Yang, Mitsutoshi Setou, Yosuke TakeiAbstract:Abstract The kinesin superfamily motor protein KIF1B has been shown to transport mitochondria. Here, we describe an isoform of KIF1B, KIF1Bβ, that is distinct from KIF1B in its cargo binding domain. KIF1B knockout mice die at birth from apnea due to nervous system defects. Death of knockout neurons in culture can be rescued by expression of the β isoform. The KIF1B heterozygotes have a defect in transporting synaptic vesicle precursors and suffer from progressive muscle weakness similar to human neuropathies. Charcot-Marie-Tooth disease type 2A was previously mapped to an interval containing KIF1B. We show that CMT2A patients contain a loss-of-function mutation in the motor domain of the KIF1B gene. This is clear indication that defects in axonal transport due to a mutated motor protein can underlie human peripheral neuropathy.
-
Charcot-Marie-Tooth Disease Type 2A Caused by Mutation in a Microtubule Motor KIF1Bβ
Cell, 2001Co-Authors: Chunjie Zhao, Junko Takita, Terunaga Nakagawa, Sen Takeda, Takao Nakata, Sumio Terada, Yosuke Tanaka, Hongwei Yang, Mitsutoshi Setou, Yosuke TakeiAbstract:The kinesin superfamily motor protein KIF1B has been shown to transport mitochondria. Here, we describe an isoform of KIF1B, KIF1Bbeta, that is distinct from KIF1B in its cargo binding domain. KIF1B knockout mice die at birth from apnea due to nervous system defects. Death of knockout neurons in culture can be rescued by expression of the beta isoform. The KIF1B heterozygotes have a defect in transporting synaptic vesicle precursors and suffer from progressive muscle weakness similar to human neuropathies. Charcot-Marie-Tooth disease type 2A was previously mapped to an interval containing KIF1B. We show that CMT2A patients contain a loss-of-function mutation in the motor domain of the KIF1B gene. This is clear indication that defects in axonal transport due to a mutated motor protein can underlie human peripheral neuropathy.
Yosuke Tanaka - One of the best experts on this subject based on the ideXlab platform.
-
KIF1Bβ mutations detected in hereditary neuropathy impair IGF1R transport and axon growth
The Journal of cell biology, 2018Co-Authors: Hironori Takahashi, Shinsuke Niwa, Yosuke Tanaka, Sotaro Ichinose, Matthew Wicklund, Nobutaka HirokawaAbstract:KIF1Bβ is a kinesin-3 family anterograde motor protein essential for neuronal development, viability, and function. KIF1Bβ mutations have previously been reported in a limited number of pedigrees of Charcot-Marie-Tooth disease type 2A (CMT2A) neuropathy. However, the gene responsible for CMT2A is still controversial, and the mechanism of pathogenesis remains elusive. In this study, we show that the receptor tyrosine kinase IGF1R is a new direct binding partner of KIF1Bβ, and its binding and transport is specifically impaired by the Y1087C mutation of KIF1Bβ, which we detected in hereditary neuropathic patients. The axonal outgrowth and IGF-I signaling of KIF1B-/- neurons were significantly impaired, consistent with decreased surface IGF1R expression. The complementary capacity of KIF1Bβ-Y1087C of these phenotypes was significantly impaired, but the binding capacity to synaptic vesicle precursors was not affected. These data have supported the relevance of KIF1Bβ in IGF1R transport, which may give new clue to the neuropathic pathogenesis.
-
the molecular motor kif1a transports the trka neurotrophin receptor and is essential for sensory neuron survival and function
Neuron, 2016Co-Authors: Yosuke Tanaka, Shinsuke Niwa, Atena Farkhondeh, Ruyun Zhou, Ming Dong, Nobutaka Hirokawa, Li WangAbstract:Summary KIF1A is a major axonal transport motor protein, but its functional significance remains elusive. Here we show that KIF1A-haploinsufficient mice developed sensory neuropathy. We found progressive loss of TrkA(+) sensory neurons in Kif1a +/− dorsal root ganglia (DRGs). Moreover, axonal transport of TrkA was significantly disrupted in Kif1a +/− neurons. Live imaging and immunoprecipitation assays revealed that KIF1A bound to TrkA-containing vesicles through the adaptor GTP-Rab3, suggesting that TrkA is a cargo of the KIF1A motor. Physiological measurements revealed a weaker capsaicin response in Kif1a +/− DRG neurons. Moreover, these neurons were hyposensitive to nerve growth factor, which could explain the reduced neuronal survival and the functional deficiency of the pain receptor TRPV1. Because phosphatidylinositol 3-kinase (PI3K) signaling significantly rescued these phenotypes and also increased Kif1a mRNA, we propose that KIF1A is essential for the survival and function of sensory neurons because of the TrkA transport and its synergistic support of the NGF/TrkA/PI3K signaling pathway.
-
charcot marie tooth disease type 2a caused by mutation in a microtubule motor KIF1Bβ
Cell, 2001Co-Authors: Chunjie Zhao, Junko Takita, Terunaga Nakagawa, Sen Takeda, Takao Nakata, Sumio Terada, Yosuke Tanaka, Hongwei Yang, Mitsutoshi Setou, Yosuke TakeiAbstract:Abstract The kinesin superfamily motor protein KIF1B has been shown to transport mitochondria. Here, we describe an isoform of KIF1B, KIF1Bβ, that is distinct from KIF1B in its cargo binding domain. KIF1B knockout mice die at birth from apnea due to nervous system defects. Death of knockout neurons in culture can be rescued by expression of the β isoform. The KIF1B heterozygotes have a defect in transporting synaptic vesicle precursors and suffer from progressive muscle weakness similar to human neuropathies. Charcot-Marie-Tooth disease type 2A was previously mapped to an interval containing KIF1B. We show that CMT2A patients contain a loss-of-function mutation in the motor domain of the KIF1B gene. This is clear indication that defects in axonal transport due to a mutated motor protein can underlie human peripheral neuropathy.
-
Charcot-Marie-Tooth Disease Type 2A Caused by Mutation in a Microtubule Motor KIF1Bβ
Cell, 2001Co-Authors: Chunjie Zhao, Junko Takita, Terunaga Nakagawa, Sen Takeda, Takao Nakata, Sumio Terada, Yosuke Tanaka, Hongwei Yang, Mitsutoshi Setou, Yosuke TakeiAbstract:The kinesin superfamily motor protein KIF1B has been shown to transport mitochondria. Here, we describe an isoform of KIF1B, KIF1Bbeta, that is distinct from KIF1B in its cargo binding domain. KIF1B knockout mice die at birth from apnea due to nervous system defects. Death of knockout neurons in culture can be rescued by expression of the beta isoform. The KIF1B heterozygotes have a defect in transporting synaptic vesicle precursors and suffer from progressive muscle weakness similar to human neuropathies. Charcot-Marie-Tooth disease type 2A was previously mapped to an interval containing KIF1B. We show that CMT2A patients contain a loss-of-function mutation in the motor domain of the KIF1B gene. This is clear indication that defects in axonal transport due to a mutated motor protein can underlie human peripheral neuropathy.
Marvin Bentley - One of the best experts on this subject based on the ideXlab platform.
-
a novel strategy to visualize vesicle bound kinesins reveals the diversity of kinesin mediated transport
Traffic, 2019Co-Authors: Gary Banker, Rui Yang, Zoe Bostick, Alex Garbouchian, Julie Luisi, Marvin BentleyAbstract:In mammals, 15 to 20 kinesins are thought to mediate vesicle transport. Little is known about the identity of vesicles moved by each kinesin or the functional significance of such diversity. To characterize the transport mediated by different kinesins, we developed a novel strategy to visualize vesicle-bound kinesins in living cells. We applied this method to cultured neurons and systematically determined the localization and transport parameters of vesicles labeled by different members of the Kinesin-1, -2, and -3 families. We observed vesicle labeling with nearly all kinesins. Only six kinesins bound vesicles that undergo long-range transport in neurons. Of these, three had an axonal bias (KIF5B, KIF5C and KIF13B), two were unbiased (KIF1A and KIF1Bβ), and one transported only in dendrites (KIF13A). Overall, the trafficking of vesicle-bound kinesins to axons or dendrites did not correspond to their motor domain preference, suggesting that on-vesicle regulation is crucial for kinesin targeting. Surprisingly, several kinesins were associated with populations of somatodendritic vesicles that underwent little long-range transport. This assay should be broadly applicable for investigating kinesin function in many cell types.
-
A novel strategy to visualize vesicle‐bound kinesins reveals the diversity of kinesin‐mediated transport
Traffic, 2019Co-Authors: Rui Yang, Gary Banker, Zoe Bostick, Alex Garbouchian, Julie Luisi, Marvin BentleyAbstract:In mammals, 15 to 20 kinesins are thought to mediate vesicle transport. Little is known about the identity of vesicles moved by each kinesin or the functional significance of such diversity. To characterize the transport mediated by different kinesins, we developed a novel strategy to visualize vesicle-bound kinesins in living cells. We applied this method to cultured neurons and systematically determined the localization and transport parameters of vesicles labeled by different members of the Kinesin-1, -2, and -3 families. We observed vesicle labeling with nearly all kinesins. Only six kinesins bound vesicles that undergo long-range transport in neurons. Of these, three had an axonal bias (KIF5B, KIF5C and KIF13B), two were unbiased (KIF1A and KIF1Bβ), and one transported only in dendrites (KIF13A). Overall, the trafficking of vesicle-bound kinesins to axons or dendrites did not correspond to their motor domain preference, suggesting that on-vesicle regulation is crucial for kinesin targeting. Surprisingly, several kinesins were associated with populations of somatodendritic vesicles that underwent little long-range transport. This assay should be broadly applicable for investigating kinesin function in many cell types.
-
a novel split kinesin assay identifies motor proteins that interact with distinct vesicle populations
Journal of Cell Biology, 2012Co-Authors: Brian Jenkins, Marvin Bentley, Julie Luisi, Helena Decker, Gary BankerAbstract:Identifying the kinesin motors that interact with different vesicle populations is a longstanding and challenging problem with implications for many aspects of cell biology. Here we introduce a new live-cell assay to assess kinesin–vesicle interactions and use it to identify kinesins that bind to vesicles undergoing dendrite-selective transport in cultured hippocampal neurons. We prepared a library of “split kinesins,” comprising an axon-selective kinesin motor domain and a series of kinesin tail domains that can attach to their native vesicles; when the split kinesins were assembled by chemical dimerization, bound vesicles were misdirected into the axon. This method provided highly specific results, showing that three Kinesin-3 family members—KIF1A, KIF13A, and KIF13B—interacted with dendritic vesicle populations. This experimental paradigm allows a systematic approach to evaluate motor–vesicle interactions in living cells.
Rui Yang - One of the best experts on this subject based on the ideXlab platform.
-
a novel strategy to visualize vesicle bound kinesins reveals the diversity of kinesin mediated transport
Traffic, 2019Co-Authors: Gary Banker, Rui Yang, Zoe Bostick, Alex Garbouchian, Julie Luisi, Marvin BentleyAbstract:In mammals, 15 to 20 kinesins are thought to mediate vesicle transport. Little is known about the identity of vesicles moved by each kinesin or the functional significance of such diversity. To characterize the transport mediated by different kinesins, we developed a novel strategy to visualize vesicle-bound kinesins in living cells. We applied this method to cultured neurons and systematically determined the localization and transport parameters of vesicles labeled by different members of the Kinesin-1, -2, and -3 families. We observed vesicle labeling with nearly all kinesins. Only six kinesins bound vesicles that undergo long-range transport in neurons. Of these, three had an axonal bias (KIF5B, KIF5C and KIF13B), two were unbiased (KIF1A and KIF1Bβ), and one transported only in dendrites (KIF13A). Overall, the trafficking of vesicle-bound kinesins to axons or dendrites did not correspond to their motor domain preference, suggesting that on-vesicle regulation is crucial for kinesin targeting. Surprisingly, several kinesins were associated with populations of somatodendritic vesicles that underwent little long-range transport. This assay should be broadly applicable for investigating kinesin function in many cell types.
-
A novel strategy to visualize vesicle‐bound kinesins reveals the diversity of kinesin‐mediated transport
Traffic, 2019Co-Authors: Rui Yang, Gary Banker, Zoe Bostick, Alex Garbouchian, Julie Luisi, Marvin BentleyAbstract:In mammals, 15 to 20 kinesins are thought to mediate vesicle transport. Little is known about the identity of vesicles moved by each kinesin or the functional significance of such diversity. To characterize the transport mediated by different kinesins, we developed a novel strategy to visualize vesicle-bound kinesins in living cells. We applied this method to cultured neurons and systematically determined the localization and transport parameters of vesicles labeled by different members of the Kinesin-1, -2, and -3 families. We observed vesicle labeling with nearly all kinesins. Only six kinesins bound vesicles that undergo long-range transport in neurons. Of these, three had an axonal bias (KIF5B, KIF5C and KIF13B), two were unbiased (KIF1A and KIF1Bβ), and one transported only in dendrites (KIF13A). Overall, the trafficking of vesicle-bound kinesins to axons or dendrites did not correspond to their motor domain preference, suggesting that on-vesicle regulation is crucial for kinesin targeting. Surprisingly, several kinesins were associated with populations of somatodendritic vesicles that underwent little long-range transport. This assay should be broadly applicable for investigating kinesin function in many cell types.
