A neuron-specific cytoplasmic dynein isoform preferentially transports TrkB signaling endosomes

Ha, Jun; Lo, Kevin W.‐H.; Myers, Kenneth R.; Carr, T. D.; Humsi, Michael K.; Rasoul, Bareza A.; Segal, Rosalind A.; Pfister, Karin

doi:10.1083/jcb.200803150

Cited by 99 publications

(126 citation statements)

References 49 publications

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“…Interestingly, Par3 was shown to be associated with the dynein complex via light intermediate chain 2 (LIC2) and contributes to the local regulation of microtubule (MT) dynamics at NIH 3T3 cell-cell contacts and also the proper positioning of the centrosome at the cell centre (Schmoranzer et al, 2009). Cells contain distinct dynein complexes distinguished by different combinations of subunit isoforms and probably make possible specific regulation of dynein motor activity and/or cargo binding (Ha et al, 2008). Here we show that dynein intermediate chain 2 (dynein IC2) interacts in an aPKC-regulated fashion with paxillin, controlling FA disassembly.…”

Section: Introductionmentioning

confidence: 79%

Binding of Dynein Intermediate Chain 2 to Paxillin controls Focal adhesion dynamics and migration.

Rossé

Boeckeler

Linch

et al. 2012

Journal of Cell Science

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SummaryIn migrating NRK cells, aPKCs control the dynamics of turnover of paxillin-containing focal adhesions (FA) determining migration rate. Using a proteomic approach (two-dimensional fluorescence difference gel electrophoresis), dynein intermediate chain 2 (dynein IC2) was identified as a protein that is phosphorylated inducibly during cell migration in a PKC-regulated manner. By gene silencing and coimmunoprecipitation studies, we show that dynein IC2 regulates the speed of cell migration through its interaction with paxillin. This interaction is controlled by serine 84 phosphorylation, which lies on the aPKC pathway. The evidence presented thus links aPKC control of migration to the dynein control of FA turnover through paxillin.

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Section: Introductionmentioning

confidence: 79%

Binding of Dynein Intermediate Chain 2 to Paxillin controls Focal adhesion dynamics and migration.

Rossé

Boeckeler

Linch

et al. 2012

Journal of Cell Science

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“…They found that dynein complexes containing IC-1B, an isoform of the intermediate chain specifically expressed in the nervous system, selectively bind to and transport neuronal TrkB-signaling endosomes. In contrast, dynein complexes containing the highly related, ubiquitously expressed IC-2C intermediate isoform do not do so (Ha et al 2008). Furthermore, TrkA signaling endosomes are not transported by IC-IB-containing dynein complexes, but bind instead to dynein complexes containing IC-2C.…”

Section: Neuronal Signaling Through Endocytosismentioning

confidence: 89%

Neuronal Signaling through Endocytosis

Cosker

Segal

2014

Cold Spring Harbor Perspectives in Biology

137

132

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The distinctive morphology of neurons, with complex dendritic arbors and extensive axons, presents spatial challenges for intracellular signal transduction. The endosomal system provides mechanisms that enable signaling molecules initiated by extracellular cues to be trafficked throughout the expanse of the neuron, allowing intracellular signals to be sustained over long distances. Therefore endosomes are critical for many aspects of neuronal signaling that regulate cell survival, axonal growth and guidance, dendritic branching, and cell migration. An intriguing characteristic of neuronal signal transduction is that endosomal trafficking enables physiological responses that vary based on the subcellular location of signal initiation. In this review, we will discuss the specialized mechanisms and the functional significance of endosomal signaling in neurons, both during normal development and in disease.

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“…In fungi and higher eukaryotic cells, dynein and kinesin might bind to the same vesicle or to each other directly, and vesicles along a microtubule often undergo bidirectional movement, which could be achieved by tug-of-war between kinesin and dynein or by other regulatory strategies (Ma and Chisholm, 2002;Ligon et al, 2004;Ha et al, 2008;Muller et al, 2008;Shubeita et al, 2008;Soppina et al, 2009;Ally et al, 2009;Hendricks et al, 2010). Nevertheless, the dynamic microtubule plus-end represents a cargo-loading site not only in fungi but also in higher eukaryotic cells (Vaughan et al, 2002;Lenz et al, 2006;Lomakin et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

The microtubule plus-end localization ofAspergillusdynein is important for dynein–early-endosome interaction but not for dynein ATPase activation

Zhang

Zhuang

Lee

et al. 2010

Journal of Cell Science

109

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Cytoplasmic dynein is a multi-subunit microtubule motor that uses the ATPase activity of its heavy chain to move towards the minus-end of a microtubule. In vivo, cytoplasmic dynein is important for the positioning of nuclei and spindles and the retrograde transport of vesicles, signaling molecules and viruses (Karki and Holzbaur, 1999;Schroer, 2004;Soldati and Schliwa, 2006;Greber and Way, 2006;Abe and Cavalli, 2008). Interestingly, although cytoplasmic dynein is a minus-enddirected motor, it accumulates at the microtubule plus-end in many cell types (Vaughan et al., 1999;Han et al., 2001;Ma and Chisholm, 2002;Lee et al., 2003;Sheeman et al., 2003;Lenz et al., 2006;Vogel et al., 2009). This accumulation at the microtubule plus-end is important for a variety of functions. For example, it might facilitate interaction with cortical proteins for spindle positioning Sheeman et al., 2003;Markus et al., 2009). In addition, because vesicles that need to undergo retrograde transport often start their journey at the plusend, the accumulation of dynein at the plus-end is thought to facilitate loading of membranous cargoes (Vaughan et al., 2002;Lenz et al., 2006).It has been found in several fungal organisms including Aspergillus nidulans, Saccharomyces cerevisiae and Ustilago maydis that the accumulation of dynein at the microtubule plusend depends on plus-end-directed kinesins (Zhang et al., 2003;Carvalho et al., 2004;Lenz et al., 2006;Caudron et al., 2008). In filamentous fungi and in neurons, kinesin 1 is important for plusend accumulation of dyenin (Zhang et al., 2003;Lenz et al., 2006;Yamada et al., 2009) and, importantly, as first discovered in U. maydis, dynein-mediated retrograde movement of early endosomes also depends on the function of kinesin 1 (Lenz et al., 2006;Abenza et al., 2009;Zekert and Fischer, 2009). These results strongly support the notion that plus-end accumulation of dynein is important for its function in vesicle trafficking. In filamentous fungi, the dynactin complex (Schroer, 2004) as well as several dynein subunits are also important for the accumulation of dynein at the microtubule plus-end (Zhang et al., 2002;Zhang et al., 2003;Zhang et al., 2008;Zhang et al., 2009;Liu et al., 2003;Lenz et al., 2006).Whether and how dynein activity is regulated at the plus-end remain to be addressed. It is thought that dynein must remain inactive at the plus-end until it interacts with cargo and/or other protein factors Sheeman et al., 2003;Zhang et al., 2003;Lenz et al., 2006;Steinberg, 2007). However, it is unclear whether dynein only gets activated at the plus-end or if it is already active before arriving at the plus-end. Here, we tested in A. nidulans whether dynein is an active ATPase before it arrives at the plus-end and whether plus-end localization is a prerequisite for activating the dynein ATPase. Our results suggest that dynein is an active ATPase before it arrives at the plus-end. The kinesin-1-mediated accumulation of dynein at the plus-ends might facilitate the interaction between early endosom...

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A neuron-specific cytoplasmic dynein isoform preferentially transports TrkB signaling endosomes

Cited by 99 publications

References 49 publications

Binding of Dynein Intermediate Chain 2 to Paxillin controls Focal adhesion dynamics and migration.

Binding of Dynein Intermediate Chain 2 to Paxillin controls Focal adhesion dynamics and migration.

Neuronal Signaling through Endocytosis

The microtubule plus-end localization ofAspergillusdynein is important for dynein–early-endosome interaction but not for dynein ATPase activation

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