Distinct cytoplasmic dynein complexes are transported by different mechanisms in axons

Susalka, Stephen J.; Hancock, William O.; Pfister, Karin

doi:10.1016/s0167-4889(00)00010-0

Cited by 49 publications

(40 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…One hypothesis is that the accessory intermediate, light intermediate, and light chain subunits of cytoplasmic dynein mediate its functional specialization. Consistent with this idea, in some eukaryotes these subunits are encoded by multiple genes that are differentially expressed and/or alternatively spliced as distinct transcripts in different tissues and cells (Gill et al, 1994;Pfister et al, 1996a;Bowman et al, 1999;Susalka et al, 2000;Tynan et al, 2000;Tai et al, 2001). In addition, the posttranslational modification of subunits may contribute to the heterogeneity of subunit composition in the dynein complex .…”

mentioning

confidence: 85%

TheDrosophilatctex-1 Light Chain Is Dispensable for Essential Cytoplasmic Dynein Functions but Is Required during Spermatid Differentiation

Serr

Newman

et al. 2004

MBoC

View full text Add to dashboard Cite

Variations in subunit composition and modification have been proposed to regulate the multiple functions of cytoplasmic dynein. Here, we examine the role of the Drosophila ortholog of tctex-1, the 14-kDa dynein light chain. We show that the 14-kDa light chain is a bona fide component of Drosophila cytoplasmic dynein and use P element excision to generate flies that completely lack this dynein subunit. Remarkably, the null mutant is viable and the only observed defect is complete male sterility. During spermatid differentiation, the 14-kDa light chain is required for the localization of a nuclear "cap" of cytoplasmic dynein and for proper attachment between the sperm nucleus and flagellar basal body. Our results provide evidence that the function of the 14-kDa light chain in Drosophila is distinct from other dynein subunits and is not required for any essential functions in early development or in the adult organism. INTRODUCTIONThe minus-end-directed microtubule motor cytoplasmic dynein has been implicated in a variety of cellular processes, including nuclear envelope breakdown, mitotic spindle assembly and orientation, chromosome movements, intracellular trafficking of organelles and mRNAs, and intraflagellar transport (reviewed in Karki and Holzbaur, 1999). The heavy chain subunit of dynein is known to provide ATPase and microtubule binding functions, and although more than one cytoplasmic dynein heavy chain has been identified, the major cytoplasmic dynein motor contains a homodimer of a single heavy chain. It remains unclear how this single cytoplasmic dynein motor is targeted to distinct organelles and cellular processes. One hypothesis is that the accessory intermediate, light intermediate, and light chain subunits of cytoplasmic dynein mediate its functional specialization. Consistent with this idea, in some eukaryotes these subunits are encoded by multiple genes that are differentially expressed and/or alternatively spliced as distinct transcripts in different tissues and cells (Gill et al., 1994;Pfister et al., 1996a;Bowman et al., 1999;Susalka et al., 2000;Tynan et al., 2000;Tai et al., 2001). In addition, the posttranslational modification of subunits may contribute to the heterogeneity of subunit composition in the dynein complex . Although the mutational analysis of the cytoplasmic dynein heavy chain has revealed a range of motor functions, the functional contribution of other individual subunits is not well understood.The present study addresses the function of the 14-kDa dynein light chain. This light chain was first identified as a cytoplasmic dynein subunit in mammalian brain (King et al., 1996a) and as an axonemal dynein subunit within the specialized inner arm dynein of the Chlamydomonas flagella (Harrison et al., 1998). In Drosophila, a molecular study of the 14-kDa light chain gene reported defective male fertility for hypomorphic alleles, but the nature of the mutations left unresolved the significance of the 14-kDa light chain in cytoplasmic dynein (Caggese et al., 2001). Sequence analysis...

show abstract

mentioning

confidence: 85%

TheDrosophilatctex-1 Light Chain Is Dispensable for Essential Cytoplasmic Dynein Functions but Is Required during Spermatid Differentiation

Serr

Newman

et al. 2004

MBoC

View full text Add to dashboard Cite

show abstract

“…Fractions containing mitochondria were identified by anti-GFP and anti-cytochrome c (CytC) staining. ends distal, anterograde transport by kinesin-1 may be required for maintaining normal levels of dynein in the distal axon (Pfister, 1999;Susalka et al, 2000). A third possibility is that kinesin-1 acts as a biochemical or biophysical activator of dynein in axons (Martin et al, 1999a).…”

Section: The Influence Of Kinesin-1 On Dynein-driven Retrograde Transmentioning

confidence: 99%

Kinesin-1 and Dynein Are the Primary Motors for Fast Transport of Mitochondria inDrosophilaMotor Axons

Pilling

Horiuchi

Lively

et al. 2006

MBoC

615

621

View full text Add to dashboard Cite

To address questions about mechanisms of filament-based organelle transport, a system was developed to image and track mitochondria in an intact Drosophila nervous system. Mutant analyses suggest that the primary motors for mitochondrial movement in larval motor axons are kinesin-1 (anterograde) and cytoplasmic dynein (retrograde), and interestingly that kinesin-1 is critical for retrograde transport by dynein. During transport, there was little evidence that force production by the two opposing motors was competitive, suggesting a mechanism for alternate coordination. Tests of the possible coordination factor P150 Glued suggested that it indeed influenced both motors on axonal mitochondria, but there was no evidence that its function was critical for the motor coordination mechanism. Observation of organelle-filled axonal swellings ("organelle jams" or "clogs") caused by kinesin and dynein mutations showed that mitochondria could move vigorously within and pass through them, indicating that they were not the simple steric transport blockades suggested previously. We speculate that axonal swellings may instead reflect sites of autophagocytosis of senescent mitochondria that are stranded in axons by retrograde transport failure; a protective process aimed at suppressing cell death signals and neurodegeneration. INTRODUCTIONOrganelle transport is central to the organization, developmental fate, and functions of asymmetric cells. A bipolar neuron is an extreme case, with the somato-dendritic region and the axon containing different sets of proteins and organelles. In general, much of the machinery for synthesizing and recycling neuronal components is clustered near the nucleus. Because an axon, often with an axial ratio of many thousands, usually contains Ͼ99% of the neuronal cytoplasm, active transport of new components away from the cell body and of spent components and trophic materials back toward the cell body is critical. Disruptions of axonal transport are thought to contribute to the pathologies of Alzheimer's, amyotrophic lateral sclerosis, and other neurodegenerative diseases (reviewed by Mandelkow and Mandelkow, 2002;Hirokawa and Takemura, 2005).Long-distance organelle transport in axons is driven by motor proteins that move along parallel microtubules whose plus ends are mostly oriented toward the axon terminal (reviewed by Hollenbeck and Saxton, 2005). There are multiple types of microtubule motors in postmitotic vertebrate neurons, including kinesins that can move toward either plus-or minus-ends and at least one cytoplasmic dynein that moves toward minus-ends (Martin et al., 1999b;Hirokawa and Takemura, 2005;Hollenbeck and Saxton, 2005). Which motors bind and move which axonal components? When multiple types of motors bind a single cargo, do they collaborate or compete, how are they regulated, and how do their combined activities generate an optimal distribution of that type of cargo?Axonal mitochondria are critical for the physiology of neurons and are particularly well suited for studying active tr...

show abstract

“…The kinesin motor unc-104/kif1a genetically interacts with tir-1 in the regulation of the AWC OFF identity Many proteins are transported by dynein/dynectin and kinesin motor proteins along microtubules to different locations within the cells (Muresan, 2000;Susalka et al, 2000). There are at least 25 dynein/dynectin-related and 23 kinesin-related genes predicted in the C. elegans genome (C. elegans Sequencing Consortium, 1998).…”

Section: Research Articlementioning

confidence: 99%

Microtubule-based localization of a synaptic calcium-signaling complex is required for left-right neuronal asymmetry in C. elegans

et al. 2011

View full text Add to dashboard Cite

SUMMARYThe axons of C. elegans left and right AWC olfactory neurons communicate at synapses through a calcium-signaling complex to regulate stochastic asymmetric cell identities called AWC ON and AWC OFF . However, it is not known how the calcium-signaling complex, which consists of UNC-43/CaMKII, TIR-1/SARM adaptor protein and NSY-1/ASK1 MAPKKK, is localized to postsynaptic sites in the AWC axons for this lateral interaction. Here, we show that microtubule-based localization of the TIR-1 signaling complex to the synapses regulates AWC asymmetry. Similar to unc-43, tir-1 and nsy-1 loss-of-function mutants, specific disruption of microtubules in AWC by nocodazole generates two AWC ON neurons. Reduced localization of UNC-43, TIR-1 and NSY-1 proteins in the AWC axons strongly correlates with the 2AWC ON phenotype in nocodazole-treated animals. We identified kinesin motor unc-104/kif1a mutants for enhancement of the 2AWC ON phenotype of a hypomorphic tir-1 mutant. Mutations in unc-104, like microtubule depolymerization, lead to a reduced level of UNC-43, TIR-1 and NSY-1 proteins in the AWC axons. In addition, dynamic transport of TIR-1 in the AWC axons is dependent on unc-104, the primary motor required for the transport of presynaptic vesicles. Furthermore, unc-104 acts non-cell autonomously in the AWC ON neuron to regulate the AWC OFF identity. Together, these results suggest a model in which UNC-104 may transport some unknown presynaptic factor(s) in the future AWC ON cell that non-cell autonomously control the trafficking of the TIR-1 signaling complex to postsynaptic regions of the AWC axons to regulate the AWC OFF identity.

show abstract

Distinct cytoplasmic dynein complexes are transported by different mechanisms in axons

Cited by 49 publications

References 69 publications

TheDrosophilatctex-1 Light Chain Is Dispensable for Essential Cytoplasmic Dynein Functions but Is Required during Spermatid Differentiation

TheDrosophilatctex-1 Light Chain Is Dispensable for Essential Cytoplasmic Dynein Functions but Is Required during Spermatid Differentiation

Kinesin-1 and Dynein Are the Primary Motors for Fast Transport of Mitochondria inDrosophilaMotor Axons

Microtubule-based localization of a synaptic calcium-signaling complex is required for left-right neuronal asymmetry in C. elegans

Contact Info

Product

Resources

About