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FEBS J,
2017]
Intraflagellar transport (IFT) is a form of motor-dependent cargo transport that is essential for the assembly, maintenance and length-control of cilia, which play critical roles in motility, sensory reception and signal transduction in virtually all eukaryotic cells. During IFT, anterograde kinesin-2 and retrograde IFT-dynein motors drive the bidirectional transport of IFT trains that deliver cargo, for example axoneme precursors such as tubulins as well as molecules of the signal transduction machinery, to their site of assembly within the cilium. Following its discovery in Chlamydomonas, IFT has emerged as a powerful model system for studying general principles of motor-dependent cargo transport and we now appreciate the diversity that exists in the mechanism of IFT within cilia of different cell-types. The absence of heterotrimeric kinesin-2 function, for example, causes a complete loss of both IFT and cilia in Chlamydomonas but following its loss in C. elegans, where its primary function is loading the IFT machinery into cilia, homodimeric kinesin-2-driven IFT persists and assembles a full-length cilium. Generally, heterotrimeric kinesin-2 and IFT-dynein motors are thought to play widespread roles as core IFT-motors whereas homodimeric kinesin-2 motors are accessory motors that mediate different functions in a broad range of cilia, in some cases contributing to axoneme assembly or the delivery of signaling molecules but in many other cases their ciliary functions, if any, remain unknown. In this review, we focus on mechanisms of motor action, motor cooperation and motor-dependent cargo delivery during IFT. This article is protected by copyright. All rights reserved.
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Biol Cell,
2018]
Epigenetic information can be inherited over multiple generations, which is termed transgenerational epigenetic inheritance (TEI). Although the mechanism(s) of TEI remains poorly understood, noncoding RNAs have been demonstrated to play important roles in TEI. In many eukaryotes, double-stranded RNA (dsRNA) triggers the silencing of cellular nucleic acids that exhibit sequence homology to the dsRNA via a process termed RNA interference (RNAi). In C. elegans, dsRNA-directed gene silencing is heritable and can persist for a number of generations after its initial induction. During the process, small RNAs and the RNAi machinery mediate the initiation, transmission, and re-establishment of the gene silencing state. In this review, we summarize our current understanding of the underlying mechanism(s) of transgenerational inheritance of RNAi in C. elegans and propose that multiple RNAi machineries may act cooperatively to promote TEI. This article is protected by copyright. All rights reserved.
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Curr Opin Cell Biol,
2010]
Genetic analysis in model organisms has recently achieved a detailed molecular description of many key cellular processes controlling embryonic morphogenesis. To understand higher order tissue morphogenesis, we now need to define how these processes become integrated across different cell groups and cell layers. Here, we review progress in this fast moving area, which was to a large degree made possible by novel imaging methods and the increasingly frequent use of modeling. Discussing examples from Caenorhabditis elegans and Drosophila embryos, two powerful and simple models, we highlight novel principles relying in part on mechanical tension, and outline the role of junctions as signal integrators.
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Curr Biol,
2006]
Recent findings indicate that the embryonic motor neurons act as gatekeepers to regulate midline crossing during development of the nematode Caenorhabditis elegans. The newly identified protein WRK-1 and ephrins cooperate to prevent longitudinal axons from crossing the midline.
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Nature Cell Biology,
2003]
In both the nematode Caenorhabditis elegans and mammals, two proteins released from the mitochondrion - apoptosis inducing factor (AIF) and endonuclease G - cooperate in executing programmed cell death. Although both factors can kill cells in a caspase-independent fashion, new studies indicate that their translocation from mitochondria depends, in part, on caspase activation. Together, these data raise new questions about the functional hierarchy between caspases, AIF and mitochondrial membrane
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Trends Genet,
1998]
Studies of sex myoblast (SM) migration in the nematode Caenorhabditis elegans have shown that multiple guidance mechanisms cooperate to ensure the accurate and reproducible targeting of the SMs. Many issues arise in the analysis of SM migration, including the action of multiple guidance mechanisms, redundant sources of guidance information, the multiple uses of molecular components, and whether factors affect cell fate determination events or the guidance mechanisms themselves. These issues are common to many cell migration events and make the analysis of SM migration instructive to our general understanding of how cell migrations are controlled.
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Curr Opin Cell Biol,
2001]
Two PDZ-domain-containing adapter-like proteins, PAR-3 and PAR-6, and a protein kinase, atypical protein kinase C (PKC), cooperate together to establish cell polarity in a variety of biological contexts. These include asymmetric cell division in early Caenorhabditis elegans embryo and Drosophila neuroblasts, as well as the establishment and maintenance of apical-basal polarity in Drosophila and mammalian epithelial cells. Recent studies on the role of this PAR-aPKC complex in epithelia[ cell polarization provide new insights into the molecular basis of epithelial junctional formation and cell polarity.
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Annu Rev Genet,
2004]
To decipher the complexity of host-pathogen interactions the widest possible range of model hosts and of analytical methods is required. As some virulence mechanisms and certain host responses have been conserved throughout evolution, even simple organisms can be used as model hosts to help our understanding of infectious diseases. The availability of molecular genetic tools and a cooperative community of researchers are pivotal to the emergence of model systems. In this review, we first summarize the genetic screens that can be used to identify pathogen virulence factors, then we present a comparative overview of existing or emerging genetically tractable host models.
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Front Biosci,
2008]
Genetic studies in Drosophila have revealed that three tumor suppressors, Discs large (Dlg), Scribble (Scrib) and Lethal giant larvae (Lgl), which localize to the basolateral region of epithelial cells, cooperatively regulate cell polarity, junction formation and cell growth in epithelial cells. Subsequent studies in Drosophila, vertebrates and C. elegans have shown the evolutionary conservation of some of their functions in epithelial cells. Also, these studies revealed the importance of antagonistic interactions between these tumor suppressors and apical polarity regulators such as Crumbs and aPKC for the establishment of apical-basal polarity with organized cell-cell junctions and regulation of cell growth in epithelial cells.
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Genes Dev,
2005]
The Ras and Notch signaling pathways are used over and over again during development to control many different biological processes. Frequently, these two signaling pathways intersect to influence common processes, but sometimes they cooperate and sometimes they antagonize each other. The Caenorhabditis elegans vulva and the Drosophila eye are two classic paradigms for understanding how Ras and Notch affect cell fates, and how the two pathways work together to control biological pattern. Recent advances in these systems reveal some of the mechanisms by which Ras and Notch can interact. Similar types of interactions in mammals may be important for determining whether and how alterations in Ras or Notch lead to cancer.