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[
Elife,
2020]
Worms with increased levels of the epigenetic mark H3K9me2 have a longer lifespan that can be passed down to future generations.
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[
Curr Top Dev Biol,
2017]
PAR-1/MARK kinases are conserved serine/threonine kinases that are essential regulators of cell polarity. PAR-1/MARK kinases localize and function in opposition to the anterior PAR proteins to control the asymmetric distribution of factors in a wide variety polarized cells. In this review, we discuss the mechanisms that control the localization and activity of PAR-1/MARK kinases, including their antagonistic interactions with the anterior PAR proteins. We focus on the role PAR-1 plays in the asymmetric division of the Caenorhabditis elegans zygote, in the establishment of the anterior/posterior axis in the Drosophila oocyte and in the control of microtubule dynamics in mammalian neurons. In addition to conserved aspects of PAR-1 biology, we highlight the unique ways in which PAR-1 acts in these distinct cell types to orchestrate their polarization. Finally, we review the connections between disruptions in PAR-1/MARK function and Alzheimer's disease and cancer.
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[
Worm Breeder's Gazette,
1994]
DNA fingerprinting in C. elegans - an approach Mark Beneckea, Jorg T. Epplenb and Einhard Schierenberga a Zoologisches Institut der Univeritat, 50923 Koln, Germany b Ruhr-Universitat, Ab1. fur Molekulare Humangenetik, 44780 Bochum, Germany
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Sci Rep,
2016]
Adapters bind motor proteins to cargoes and therefore play essential roles in Kinesin-1 mediated intracellular transport. The regulatory mechanisms governing adapter functions and the spectrum of cargoes recognized by individual adapters remain poorly defined. Here, we show that cargoes transported by the Kinesin-1 adapter FEZ1 are enriched for presynaptic components and identify that specific phosphorylation of FEZ1 at its serine 58 regulatory site is mediated by microtubule affinity-regulating kinases (MARK/PAR-1). Loss of MARK/PAR-1 impairs axonal transport, with adapter and cargo abnormally co-aggregating in neuronal cell bodies and axons. Presynaptic specializations are markedly reduced and distorted in FEZ1 and MARK/PAR-1 mutants. Strikingly, abnormal co-aggregates of unphosphorylated FEZ1, Kinesin-1 and its putative cargoes are present in brains of transgenic mice modelling aspects of Alzheimer's disease, a neurodegenerative disorder exhibiting impaired axonal transport and altered MARK activity. Our findings suggest that perturbed FEZ1-mediated synaptic delivery of proteins arising from abnormal signalling potentially contributes to the process of neurodegeneration.
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[
Nat Commun,
2013]
Hallmarks of criticality, such as power-laws and scale invariance, have been empirically found in cortical-network dynamics and it has been conjectured that operating at criticality entails functional advantages, such as optimal computational capabilities, memory and large dynamical ranges. As critical behaviour requires a high degree of fine tuning to emerge, some type of self-tuning mechanism needs to be invoked. Here we show that, taking into account the complex hierarchical-modular architecture of cortical networks, the singular critical point is replaced by an extended critical-like region that corresponds--in the jargon of statistical mechanics--to a Griffiths phase. Using computational and analytical approaches, we find Griffiths phases in synthetic hierarchical networks and also in empirical brain networks such as the human connectome and that of Caenorhabditis elegans. Stretched critical regions, stemming from structural disorder, yield enhanced functionality in a generic way, facilitating the task of self-organizing, adaptive and evolutionary mechanisms selecting for criticality.
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Mol Cell,
2013]
In this issue of Molecular Cell, Castellano-Pozo etal. (2013) describe a connection between R loop structures and histone 3 S10 phosphorylation (H3S10P), a mark of chromatin compaction. Their results constitute asignificant advance in our understanding of the role of R loops in genomic instability.
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Curr Biol,
2010]
The small GTPases Rab5 and Rab7 mark temporally distinct but sequentially connected stages in phagosome maturation, but the mechanism underlying the transition between these stages has been unclear. Recent studies in Caenorhabditis elegans have now uncovered a new protein complex that connects Rab5 to Rab7.
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Trends Genet,
2001]
Four recent papers mark a major shift in functional genomic analysis for multicellular organisms. RNA-mediated interference was applied to inactivate individual genes systematically on a genomic scale. These studies subjected a third of the genes in the genome of Caenorhabditis elegans to reverse genetic analysis.
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[
Worm Breeder's Gazette,
1990]
The CGC Bibliography has been translated into a couple of programs other than dBase by various worm people. David Barker and Andy Fire both have sent HyperCard versions to the CGC and Mark Blaxter has sent us a version in FileMaker 2.0. None of these is perfectly up-to-date, so you'll have to be somewhat familiar with the programs to add new references. The data files are available free from the CGC; to get yours, just send a blank 3.5' diskette to Mark Edgley at the CGC with a request letter. In addition, Lew Jacobson has translated the bibliography into a DOS program called Memory Mate and he is willing to distribute the data file to anyone who sends him a blank 5.25' 360 Kb diskette. Memory Mate can be operated as a TSR and called up with a hotkey from the middle of a word processor or other program. Addresses for Mark and Lew can be found in the Subscriber Directory Update in this issue.
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Development,
2019]
The MARK/PAR-1 family of kinases are conserved regulators of cell polarity that share a conserved C-terminal kinase-associated domain (KA1). Localization of MARK/PAR-1 kinases to specific regions of the cell cortex is a hallmark of polarized cells. In <i>C. elegans</i> zygotes, PAR-1 localizes to the posterior cortex under the influence of another polarity kinase, aPKC/PKC-3. Here we report that asymmetric localization of PAR-1 protein is not essential, and that PAR-1 kinase activity is also regulated spatially. We find that, as in human MARK1, the PAR-1 KA1 domain is an auto-inhibitory domain that suppresses kinase activity. Auto-inhibition by the KA1 domain functions in parallel with phosphorylation by PKC-3 to suppress PAR-1 activity in the anterior cytoplasm. The KA1 domain also plays an additional role essential for germ plasm maintenance and fertility. Our findings suggest that modular regulation of kinase activity by redundant inhibitory inputs contributes to robust symmetry breaking by MARK/PAR-1 kinases in diverse cell types.