Targeted Disruption of Mouse Conventional Kinesin Heavy Chain kif5B, Results in Abnormal Perinuclear Clustering of Mitochondria

Tanaka, Yosuke; Kanai, Yoshiyuki; Okada, Yasushi; Nonaka, Shigenori; Takeda, Sén; Harada, Akira; Hirokawa, Nobutaka

doi:10.1016/s0092-8674(00)81459-2

Cited by 601 publications

(574 citation statements)

References 75 publications

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“…Whole-body pathological evaluation at gross from specialized molecular machinery in neurons, the cell type in which mitochondria are likely to travel longer distances than in any other type of cell ( 48 ). This interpretation is supported by the close resemblance of mitochondrial distribution in our MyD88-5 -overexpressing cells and in cells in which mitochondrial traffi c along microtubules was disrupted via interference with the motor protein kinesin by genetic disruption ( 49 ) or TNF treatment ( 50 ). Moreover, overexpression of proteins involved in mitochondrial fi ssion, fusion, and traffi cking decreased mitochondrial movement, promoted a rounded rather than elongated mitochondrial morphology and increased the cells ' susceptibility to apoptosis ( 48, 51 -57 ).…”

Section: Myd88-5 Is Associated With Mitochondriamentioning

confidence: 54%

MyD88-5 links mitochondria, microtubules, and JNK3 in neurons and regulates neuronal survival

Kim¹,

Zhou²,

Qian³

et al. 2007

J Cell Biol

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Section: Myd88-5 Is Associated With Mitochondriamentioning

confidence: 54%

MyD88-5 links mitochondria, microtubules, and JNK3 in neurons and regulates neuronal survival

Kim¹,

Zhou²,

Qian³

et al. 2007

J Cell Biol

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“…92). In mammalian cells, a rigor mutant of kinesin-1 blocks plus-end-directed lysosome movement 93 , and targeted disruption of the gene that encodes kinesin-1 impairs lysosome dispersion 94 . Last, an intriguing finding is that KIF2β, a splice variant of KIF2 that is found in non-neuronal cells and a member of the kinesin-13 family, supposedly drives plus-end-directed transport of lysosomes 95 .…”

Section: Outbound Trafficmentioning

confidence: 99%

Powering membrane traffic in endocytosis and recycling

Soldati

Schliwa

2006

Nat Rev Mol Cell Biol

312

279

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| Early in evolution, the diversification of membrane-bound compartments that characterize eukaryotic cells was accompanied by the elaboration of molecular machineries that mediate intercompartmental communication and deliver materials to specific destinations. Molecular motors that move on tracks of actin filaments or microtubules mediate the movement of organelles and transport between compartments. The subjects of this review are the motors that power the transport steps along the endocytic and recycling pathways, their modes of attachment to cargo and their regulation.The emergence of eukaryotic cells was accompanied by the development of endomembrane systems that compartmentalize biochemical pathways and biosynthetic processes. An evolutionary trend towards increasing complexity and subcellular specialization necessitated the development of machineries for intercompartmental communication. Molecular assemblies evolved to confer specificity to the interactions of donor and acceptor compartments (budding, sorting, tethering and fusion). Cytoskeletal polymers such as actin filaments and microtubules, which help segregate genetic material and determine cell shape and subcellular architecture, were co-opted as tracks for transport. In animal cells, microtubules support long-range transport, whereas the more flexible actin filaments serve short-range movements both near the cell periphery and in the cell interior. Also, actin filaments can be woven into dense networks of short fibres through the action of crosslinkers and branchpromoting complexes. On the other hand, in many plant cells, bundled actin filaments can form extended tracks for long-distance transport. Owing to the gel-like nature of the cytoplasm, the Brownian movement of organelles is severely restricted and cargoes have to be transported to their destinations at the expense of energy. Furthermore, seemingly random, but motor-dependent, movement is proposed to increase the probability of vesicle collisions and therefore promote fusion events. Movement is powered by three ATP-dependent motors: myosin, kinesin and dynein. Over the course of eukaryotic evolution, these motors have diversified into a large number of families with specific tasks (FIG. 1).Here, we review the involvement of molecular motors in the movement of endosomes and in vesicular trafficking along the endocytic and recycling pathways. These pathways are summarized in FIG. 2. We do not, however,

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“…For example, in a study of vesicle/ tubule transport in the recycling pathway, antibody inhibition of KHC blocked brefeldin A-induced movement of Golgi membranes into the ER in cultured NRK cells (Lippincott-Schwartz et al, 1995). Conversely, antisense oligonucleotide inhibition of KHC in cultured rat astrocytes (Feiguin et al, 1994) and gene disruption in cultured mouse extraembryonic cells (Tanaka et al, 1998) did not prevent brefeldin A-induced Golgi-to-ER membrane transfer. With regard to Golgi-to-plasma membrane vesicle transport, antisense oligonucleotide inhibition of KHC in cultured vertebrate neurons impaired delivery of vesicles containing certain synaptic proteins to axon terminals (Ferreira et al, 1992).…”

Section: Discussionmentioning

confidence: 86%

“…In contrast, antibody inhibition of KHC in sea urchin embryonic cells (Wright et al, 1993) or gene disruption in mouse extraembryonic cells (Tanaka et al, 1998) had no dramatic effects on ER organization. Antibody inhibition of KHC in human fibroblasts (Rodionov et al, 1993) and gene disruption in mouse extraembryonic cells (Tanaka et al, 1998) caused mitochondria, which are normally dispersed throughout the cytoplasm, to cluster near the cell center. However, no effect on mitochondrial distribution was seen in rat astrocytes injected with Khc antisense oligonucleotides (Feiguin et al, 1994) or in mutant strains of C. elegans (Hall et al, 1991) and fungi (Lehmler et al, 1997;Seiler et al, 1997).…”

mentioning

confidence: 75%

Clonal Tests of Conventional Kinesin Function during Cell Proliferation and Differentiation

Brendza

Sheehan

Turner

et al. 2000

MBoC

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Null mutations in the Drosophila Kinesin heavy chain gene (Khc), which are lethal during the second larval instar, have shown that conventional kinesin is critical for fast axonal transport in neurons, but its functions elsewhere are uncertain. To test other tissues, single imaginal cells in young larvae were rendered null for Khc by mitotic recombination. Surprisingly, the null cells produced large clones of adult tissue. The rates of cell proliferation were not reduced, indicating that conventional kinesin is not essential for cell growth or division. This suggests that in undifferentiated cells vesicle transport from the Golgi to either the endoplasmic reticulum or the plasma membrane can proceed at normal rates without conventional kinesin. In adult eye clones produced by null founder cells, there were some defects in differentiation that caused mild ultrastructural changes, but they were not consistent with serious problems in the positioning or transport of endoplasmic reticulum, mitochondria, or vesicles. In contrast, defective cuticle deposition by highly elongated Khc null bristle shafts suggests that conventional kinesin is critical for proper secretory vesicle transport in some cell types, particularly ones that must build and maintain long cytoplasmic extensions. The ubiquity and evolutionary conservation of kinesin heavy chain argue for functions in all cells. We suggest interphase organelle movements away from the cell center are driven by multilayered transport mechanisms; that is, individual organelles can use kinesin-related proteins and myosins, as well as conventional kinesin, to move toward the cell periphery. In this case, other motors can compensate for the loss of conventional kinesin except in cells that have extremely long transport tracks. INTRODUCTIONVesicle transport is important in eukaryotic cells for the addition of material to the plasma membrane, for secretion, and for cell polarity. Active vesicle transport is thought to be driven by mechanochemical enzymes (motor proteins). Motors attach to vesicle membranes and then use ATP hydrolysis to drive unidirectional movement along polar cytoskeletal filaments. Characterized members of the myosin family of motors move toward the barbed or fast-growing ends of actin filaments with the exception of myosin VI, which moves toward the pointed or slow-growing ends (Wells et al., 1999) (reviewed by Sellers and Goodson, 1995). Actin filaments in undifferentiated and in some differentiated cell types are highly concentrated in the cortex (WatermanStorer et al., 1998; reviewed by Cramer, 1999). Cytoplasmic myosins may therefore be important for anchoring or moving vesicles when they are near the plasma membrane (Fath et al., 1994). Motors in the kinesin and dynein families move along microtubules. Characterized dyneins and members of the C-terminal kinesin subfamily move toward microtubule minus ends, whereas other kinesins that act as motors move toward microtubule plus ends (reviewed by Vale and Fletterick, 1997;Hirokawa, 1998;Goldstein and Ya...

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Targeted Disruption of Mouse Conventional Kinesin Heavy Chain kif5B, Results in Abnormal Perinuclear Clustering of Mitochondria

Cited by 601 publications

References 75 publications

MyD88-5 links mitochondria, microtubules, and JNK3 in neurons and regulates neuronal survival

MyD88-5 links mitochondria, microtubules, and JNK3 in neurons and regulates neuronal survival

Powering membrane traffic in endocytosis and recycling

Clonal Tests of Conventional Kinesin Function during Cell Proliferation and Differentiation

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