Kinesin Light Chains Are Essential for Axonal Transport in <i>Drosophila </i>

Gindhart, Joseph G.; Desai, Chand; Beushausen, Sven; Zinn, Kai; Goldstein, Lawrence S.B.

doi:10.1083/jcb.141.2.443

Cited by 169 publications

(187 citation statements)

References 101 publications

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“…BmKinesin-1 belongs to Kinesin-1 subfamily, and is homologous to DmKHC in Drosophila and KIF5 in mammals. In Drosophila, mutations of both and light chain disrupt axonal transport, causing motor neuron disease phenotypes [39]. In mouse, BmKinesin-1's homologue KIF5 has three members, namely, neuron-specific KIF5A and KIF5C, and ubiquitous KIF5B.…”

Section: Discussionmentioning

confidence: 99%

Characterization of kinesin-like proteins in silkworm posterior silkgland cells

et al. 2010

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Section: Discussionmentioning

confidence: 99%

Characterization of kinesin-like proteins in silkworm posterior silkgland cells

et al. 2010

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“…Several experiments support such a role. In Drosophila KLC mutants, large aggregates ("organelle jams") accumulate in axons, resulting from a block in axonal transport (9). Also, anti-KLC antibodies inhibit fast axonal transport without affecting microtubule binding or ATPase activity in vitro and cause release of purified membrane vesicles from kinesin (14).…”

Section: Discussionmentioning

confidence: 99%

“…KLCs have been suggested to bind cargo and to regulate the activity of KHCs. Clues as to possible functions and the domains involved came from sequence comparisons and genetic analysis of KLCs that were cloned from Caenorhabditis elegans (6), sea urchin (7), squid (8), Drosophila (9,10), and mammals (11)(12)(13)(14)(15)(16). In mouse, KLC1, a largely neuronal form of KLC, and the ubiquitous KLC2 have been identified (12).…”

mentioning

confidence: 99%

Association of Kinesin Light Chain with Outer Dense Fibers in a Microtubule-independent Fashion

Bhullar

Zhang

Junco

et al. 2003

Journal of Biological Chemistry

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Conventional kinesin I motor molecules are heterotetramers consisting of two kinesin light chains (KLCs) and two kinesin heavy chains. The interaction between the heavy and light chains is mediated by the KLC heptad repeat (HR), a leucine zipper-like motif. Kinesins bind to microtubules and are involved in various cellular functions, including transport and cell division. We recently isolated a novel KLC gene, klc3. klc3 is the only known KLC expressed in post-meiotic male germ cells. A monoclonal anti-KLC3 antibody was developed that, in immunoelectron microscopy, detects KLC3 protein associated with outer dense fibers (ODFs), unique structural components of sperm tails. No significant binding of KLC3 with microtubules was observed with this monoclonal antibody. In vitro experiments showed that KLC3-ODF binding occurred in the absence of kinesin heavy chains or microtubules and required the KLC3 HR. ODF1, a major ODF protein, was identified as the KLC3 binding partner. The ODF1 leucine zipper and the KLC3 HR mediated the interaction. These results identify and characterize a novel interaction between a KLC and a non-microtubule macromolecular structure and suggest that KLC3 could play a microtubule-independent role during formation of sperm tails.

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“…Known fast-axonal-transport cargoes, such as vesicle-associated synaptic terminal proteins and mitochondria, accumulate in axonal swellings caused by mutation of kinesin-1 or dynein subunits (Hurd and Saxton, 1996;Gindhart et al, 1998;Bowman et al, 1999;Martin et al, 1999). Slow-transport materials, such as tubulin, appear evenly distributed in the nerves of such motor mutants and do not accumulate in axonal swellings (Hurd and Saxton, 1996).…”

Section: Ena Does Not Behave Like a Fast-axonal-transport Cargomentioning

confidence: 99%

Abl Tyrosine Kinase and Its Substrate Ena/VASP Have Functional Interactions with Kinesin-1

Martin

Ahern-Djamali

Hoffmann

et al. 2005

MBoC

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Relatively little is known about how microtubule motors are controlled or about how the functions of different cytoskeletal systems are integrated. A yeast two-hybrid screen for proteins that bind to Drosophila Enabled (Ena), an actin polymerization factor that is negatively regulated by Abl tyrosine kinase, identified kinesin heavy chain (Khc), a member of the kinesin-1 subfamily of microtubule motors. Coimmunoprecipitation from Drosophila cytosol confirmed a physical interaction between Khc and Ena. Kinesin-1 motors can carry organelles and other macromolecular cargoes from neuronal cell bodies toward terminals in fast-axonal-transport. Ena distribution in larval axons was not affected by mutations in the Khc gene, suggesting that Ena is not itself a fast transport cargo of Drosophila kinesin-1. Genetic interaction tests showed that in a background sensitized by reduced Khc gene dosage, a reduction in Abl gene dosage caused distal paralysis and axonal swellings. A concomitant reduction in ena dosage rescued those defects. These results suggest that Ena/VASP, when not inhibited by the Abl pathway, can bind Khc and reduce its transport activity in axons. INTRODUCTIONThe activities of the F-actin and microtubule cytoskeletons are linked in cellular processes such as secretion, cytokinesis, and axon outgrowth, but relatively little is known about mechanisms that coordinate the activities of the two filament systems. The nonreceptor tyrosine kinase Abl, aberrant forms of which are implicated in human leukemia, influences axon outgrowth and other F-actin-dependent processes (Woodring et al., 2003;Hernandez et al., 2004). Recent work suggests that Abl also influences microtubule polymerization in the axon growth cone via interactions with Orbit and that a mouse Abl-related protein, Arg, can crosslink F-actin with microtubules in the cell periphery (Lee et al., 2004;Miller et al., 2004). In part, the influence of Abl on F-actin-dependent processes is mediated by its regulatory interaction with Ena/VASP proteins, which can modulate actin filament length, branching pattern, and bundle formation (reviewed by Krause et al., 2003;Kwiatkowski et al., 2003). Ena/VASP proteins have three conserved regions. The N-terminal EVH1 domain (133 amino acids, Gertler et al., 1996) can bind the focal-adhesion proteins vinculin and zyxin, as well as the growth-cone guidance receptor Robo/ Sax3. The central proline-rich region can bind profilin, which facilitates the addition of G-actin monomers to F-actin plusends. It can also bind Abl and other SH3-domain proteins. The C-terminal EVH2 domain (226 amino acids, Gertler et al., 1996) has both G-and F-actin binding sites and has been shown to mediate Ena/VASP multimerization (reviewed by Krause et al., 2003;Kwiatkowski et al., 2003).In Drosophila development, Ena and Abl are known to have an antagonistic relationship. Zygotic mutations in the ena or Abl gene cause axon growth-cone guidance defects and lethality, but normal axon guidance and viability can be restored by combining ena and Ab...

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Kinesin Light Chains Are Essential for Axonal Transport in Drosophila

Cited by 169 publications

References 101 publications

Characterization of kinesin-like proteins in silkworm posterior silkgland cells

Characterization of kinesin-like proteins in silkworm posterior silkgland cells

Association of Kinesin Light Chain with Outer Dense Fibers in a Microtubule-independent Fashion

Abl Tyrosine Kinase and Its Substrate Ena/VASP Have Functional Interactions with Kinesin-1

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