Cell Biology This Week
This week, many papers
caught my eye so I’m trying a different approach, i.e. writing less about
more. If you prefer one style to the
other, please feel free to leave a comment.
There have been several papers recently describing different mechanisms by which proteins enter the primary cilium. There have been tantalizing clues in the literature (for example Fan et al.) that have indicated functions for nuclear import machinery in targeting proteins to the cilium. Dishinger et al. now provide definitive evidence for this idea through their analysis of ciliary targeting of the intraflagellar transport motor Kif17. Their results support a model in which a complex of Kif17 and importin beta2 in the cytoplasm crosses into the cilium where the presence of RanGTP triggers their dissociation. Elsewhere, Hu et al. show that a septin diffusion barrier controls the entry of proteins into the cilium. And finally, Jin et al. show that the BBSome, together with the small GTPase Arl6, assemble a coat complex similar to the COPII or clathrin coats, to shepherd proteins into the cilium. It’s been busy times for this organelle! It will be interesting to see whether and how these different targeting methods intersect and how the roles of importins and septins at the cilium are balanced with their other functions in the cell.Although we know that microRNAs regulate almost every physiological and disease process, we are just now starting to uncover the details of the cellular mechanisms by which microRNAs exert their control. Li et al. show that the most abundant cardiac microRNA miR-1—previously shown to be involved in cardiac hypertrophy—targets the actin-binding protein twinfilin (specifically TWF1). In experimentally-induced cardiac hypertrophy in rats, miR-1 is downregulated and twinfilin levels are increased. In fact, overexpression of twinfilin causes hypertrophy. Further analysis of the cardiac cytoskeleton will reveal how alterations in the cellular architecture of cardiomyocytes contribute to this diseased state.
Moving on to more biophysical considerations, Block et al. show that the presence of a cell edge is sufficient to activate EGFR signaling to promote wound healing in epithelial sheets. Meanwhile, Connelly et al. examine how cell shape affects differentiation of human epidermal skin cells. They find that when they restrict cell spreading (using micropatterned substrates), the actin cytoskeleton and serum growth factors trigger transcriptional responses to promote differentiation.
Finally, I want to point your attention to a study that is a nice example of how both environmental and genetic insults can work together to contribute to disease and that also has obvious therapeutic implications. Cadwell et al. show that in a mouse model for Crohn’s disease (carrying a mutation of the Crohn’s susceptibility gene Atg16L1—for more information about this gene, see the review by Saitoh and Akira), are more likely to develop symptoms and pathology of the disease, in response to a toxin, if they have been infected by particular strain of murine norovirus (MNV). Furthermore, commensal gut bacteria are also involved in disease progression. The presence of multiple contributing factors could explain the variation in symptoms and susceptibility in patients.
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