UNC-83 coordinates kinesin-1 and dynein activities at the nuclear envelope during nuclear migration

Fridolfsson, Heidi N.; Ly, Nina; Meyerzon, Marina; Starr, Daniel A.

doi:10.1016/j.ydbio.2009.12.004

Cited by 122 publications

(144 citation statements)

References 66 publications

(96 reference statements)

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“…The concept of nuclear positioning by gliding along microtubules is supported by previous studies demonstrating an interaction of kinesin and dynein-dynactin motor complexes with mammalian nesprins 1, 2 and 4, and with the related KASH-domain proteins ZYG-12 and UNC-83 in C. elegans (Malone et al, 2003;Roux et al, 2009;Zhang et al, 2009;Fridolfsson et al, 2010;Yu et al, 2011;Holzbaur, 2012, 2015). In myotubes, we propose that this interaction is indirect, mediated by nuclear-envelope-bound centrosome proteins, because the depletion of the centrosome protein PCM-1 induces loss of dynactin and kinesin subunits from the nuclear surface.…”

Section: Discussionmentioning

confidence: 85%

“…In various studies on non-muscular cells, nesprins have been implied to interact with the actin cytoskeleton (Starr and Han, 2002;Zhen et al, 2002;Padmakumar et al, 2004). In addition, nesprins and related proteins have been shown to interact with components of the microtubule network, such as kinesin, dynein and dynactin, and with the centrosome (Malone et al, 2003;Roux et al, 2009;Zhang et al, 2009;Zhou et al, 2009;Fridolfsson et al, 2010;Yu et al, 2011;Holzbaur, 2012, 2015). Several groups have reported that proteins of the centrosome, such as PCM-1, pericentrin and γ-tubulin, are relocated from the pericentriolar material to the nuclear envelope upon onset of myoblast differentiation, and that a substantial amount of microtubules grow from the nuclear surface following this reorganization (Tassin et al, 1985a;Bugnard et al, 2005;Srsen et al, 2009;Fant et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

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Nuclear alignment in myotubes requires centrosome proteins recruited by nesprin-1

Espigat-Georger

Dyachuk

Chemin

et al. 2016

Journal of Cell Science

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Myotubes are syncytial cells generated by fusion of myoblasts. Among the numerous nuclei in myotubes of skeletal muscle fibres, the majority are equidistantly positioned at the periphery, except for clusters of multiple nuclei underneath the motor endplate. The correct positioning of nuclei is thought to be important for muscle function and requires nesprin-1 (also known as SYNE1), a protein of the nuclear envelope. Consistent with this, mice lacking functional nesprin-1 show defective nuclear positioning and present aspects of Emery-Dreifuss muscular dystrophy. In this study, we perform small interfering RNA (siRNA) experiments in C2C12 myoblasts undergoing differentiation, demonstrating that the positioning of nuclei requires PCM-1, a protein of the centrosome that relocalizes to the nuclear envelope at the onset of differentiation in a manner that is dependent on the presence of nesprin-1. PCM-1 itself is required for recruiting proteins of the dynein-dynactin complex and of kinesin motor complexes. This suggests that microtubule motors that are attached to the nuclear envelope support the movement of nuclei along microtubules, to ensure their correct positioning in the myotube.

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Section: Discussionmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Nuclear alignment in myotubes requires centrosome proteins recruited by nesprin-1

Espigat-Georger

Dyachuk

Chemin

et al. 2016

Journal of Cell Science

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“…Furthermore, Rab6B-BicD1 interaction regulates retrograde membrane transport in human neurites (Wanschers et al, 2007). Fly and worm Bic-D genes are also involved in nuclear migration in photoreceptors, oocytes and hypodermal precursor cells (Swan et al, 1999;Swan and Suter, 1996;Fridolfsson et al, 2010), and Bic-D also dynamically regulates transport of lipid droplets (Larsen et al, 2008). Given the involvement of Bic-D in the localization of surprisingly diverse cargoes, we searched for adaptor proteins that mediate cargo binding as well as for novel cargo molecules.…”

Section: Introductionmentioning

confidence: 99%

Clathrin heavy chain plays multiple roles in polarizing the Drosophila oocyte downstream of Bic-D

et al. 2014

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Bicaudal-D (Bic-D), Egalitarian (Egl), microtubules and their motors form a transport machinery that localizes a remarkable diversity of mRNAs to specific cellular regions during oogenesis and embryogenesis. Bic-D family proteins also promote dynein-dependent transport of Golgi vesicles, lipid droplets, synaptic vesicles and nuclei. However, the transport of these different cargoes is still poorly understood. We searched for novel proteins that either mediate Bic-Ddependent transport processes or are transported by them. Clathrin heavy chain (Chc) co-immunopurifies with Bic-D in embryos and ovaries, and a fraction of Chc colocalizes with Bic-D. Both proteins control posterior patterning of the Drosophila oocyte and endocytosis. Although the role of Chc in endocytosis is well established, our results show that Bic-D is also needed for the elevated endocytic activity at the posterior of the oocyte. Apart from affecting endocytosis indirectly by its role in osk mRNA localization, Bic-D is also required to transport Chc mRNA into the oocyte and for transport and proper localization of Chc protein to the oocyte cortex, pointing to an additional, more direct role of Bic-D in the endocytic pathway. Furthermore, similar to Bic-D, Chc also contributes to proper localization of osk mRNA and to oocyte growth. However, in contrast to other endocytic components and factors of the endocytic recycling pathway, such as Rabenosyn-5 (Rbsn-5) and Rab11, Chc is needed during early stages of oogenesis (from stage 6 onwards) to localize osk mRNA correctly. Moreover, we also uncovered a novel, presumably endocytosis-independent, role of Chc in the establishment of microtubule polarity in stage 6 oocytes.

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“…LC8 is conserved throughout eukaryotic genomes (5). As a part of the dynein motor, LC8 is important for fundamental cellular processes, such as tubulin minus-enddirected intracellular transport, chromatid separation during mitosis, and nuclear migration (6), as well as flagellum-specific functions, namely, motility, intraflagellar transport (7), and ciliogenesis (8,9). While not essential in Saccharomyces cerevisiae (10), mutation or knockdown of LC8 is embryonic lethal in animals (8,9,11,12).…”

mentioning

confidence: 99%

Dynein Light Chain LC8 Is Required for RNA Polymerase I-Mediated Transcription in Trypanosoma brucei, Facilitating Assembly and Promoter Binding of Class I Transcription Factor A

Kirkham

Park

Nguyen

et al. 2016

Molecular and Cellular Biology

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Dynein light chain LC8 is highly conserved among eukaryotes and has both dynein-dependent and dynein-independent functions. Interestingly, LC8 was identified as a subunit of the class I transcription factor A (CITFA), which is essential for transcription by RNA polymerase I (Pol I) in the parasite Trypanosoma brucei. Given that LC8 has never been identified with a basal transcription factor and that T. brucei relies on RNA Pol I for expressing the variant surface glycoprotein (VSG), the key protein in antigenic variation, we investigated the CITFA-specific role of LC8. Depletion of LC8 from mammalian-infective bloodstream trypanosomes affected cell cycle progression, reduced the abundances of rRNA and VSG mRNA, and resulted in rapid cell death. Sedimentation analysis, coimmunoprecipitation of recombinant proteins, and bioinformatic analysis revealed an LC8 binding site near the N terminus of the subunit CITFA2. Mutation of this site prevented the formation of a CITFA2-LC8 heterotetramer and, in vivo, was lethal, affecting assembly of a functional CITFA complex. Gel shift assays and UV cross-linking experiments identified CITFA2 as a promoter-binding CITFA subunit. Accordingly, silencing of LC8 or CITFA2 resulted in a loss of CITFA from RNA Pol I promoters. Hence, we discovered an LC8 interaction that, unprecedentedly, has a basal function in transcription. Dynein light chain LC8 was originally discovered as a component of the outer arm axonemal dynein in Chlamydomonas reinhardtii (1) but was later found to be present also in cytoplasmic dyneins 1 and 2 (2-4). LC8 is conserved throughout eukaryotic genomes (5). As a part of the dynein motor, LC8 is important for fundamental cellular processes, such as tubulin minus-enddirected intracellular transport, chromatid separation during mitosis, and nuclear migration (6), as well as flagellum-specific functions, namely, motility, intraflagellar transport (7), and ciliogenesis (8, 9). While not essential in Saccharomyces cerevisiae (10), mutation or knockdown of LC8 is embryonic lethal in animals (8,9,11,12). Given that LC8 is more conserved between species than other components of the dynein motor and that LC8 is present in organisms which lack a dynein motor, it was likely that LC8 had nondynein functions (3, 5). LC8 has since been shown to interact with several different proteins and to affect various cellular processes, including protein localization and stability, transcription regulation, and apoptosis (13-15).At physiological pH, LC8 exists almost exclusively as a dimer (16, 17), interacting with partner proteins via two identical sites generated at the dimer interface which bind to diverse short, linear motifs (16,18,19). LC8 promotes the dimerization of its binding partners through aligning dimerization domains present in the partner protein (13,(20)(21)(22). While it was previously hypothesized that LC8 functions as a linker, allowing attachment of the dynein motor to its cargo, the emerging view is that interaction with LC8 induces dimerization, imparting new s...

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UNC-83 coordinates kinesin-1 and dynein activities at the nuclear envelope during nuclear migration

Cited by 122 publications

References 66 publications

Nuclear alignment in myotubes requires centrosome proteins recruited by nesprin-1

Nuclear alignment in myotubes requires centrosome proteins recruited by nesprin-1

Clathrin heavy chain plays multiple roles in polarizing the Drosophila oocyte downstream of Bic-D

Dynein Light Chain LC8 Is Required for RNA Polymerase I-Mediated Transcription in Trypanosoma brucei, Facilitating Assembly and Promoter Binding of Class I Transcription Factor A

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