Mechanisms of mammalian ciliary motility: Insights from primary ciliary dyskinesia genetics

Motile cilia and flagella are organelles that, historically, have been poorly understood and inadequately investigated. However, cilia play critical roles in fluid clearance in the respiratory system and the brain, and flagella are required for sperm motility. Genetic studies involving human patients and mouse models of primary ciliary dyskinesia over the last decade have uncovered a number of important ciliary proteins and have begun to elucidate the mechanisms underlying ciliary motility. When combined with genetic, biochemical, and cell biological studies in Chlamydomonas reinhardtii, these mammalian genetic analyses begin to reveal the mechanisms by which ciliary motility is regulated.     

The role of MAPK signalling pathways in the response to endoplasmic reticulum stress

Perturbations in endoplasmic reticulum (ER) homeostasis, including depletion of Ca^2 + or altered redox status, induce ER stress due to protein accumulation, misfolding and oxidation. This activates the unfolded protein response (UPR) to re-establish the balance between ER protein folding capacity and protein load, resulting in cell survival or, following chronic ER stress, promotes cell death. The mechanisms for the transition between adaptation to ER stress and ER stress-induced cell death are still being understood. However, the identification of numerous points of cross-talk between the UPR and mitogen-activated protein kinase (MAPK) signalling pathways may contribute to our understanding of the consequences of ER stress. Indeed, the MAPK signalling network is known to regulate cell cycle progression and cell survival or death responses following a variety of stresses. In this article, we review UPR signalling and the activation of MAPK signalling pathways in response to ER stress. In addition, we highlight components of the UPR that are modulated in response to MAPK signalling and the consequences of this cross-talk. We also describe several diseases, including cancer, type II diabetes and retinal degeneration, where activation of the UPR and MAPK signalling contribute to disease progression and highlight potential avenues for therapeutic intervention. This article is part of a Special Issue entitled: Calcium Signaling In Health and Disease. Guest Editors: Geert Bultynck, Jacques Haiech, Claus W. Heizmann, Joachim Krebs, and Marc Moreau.     

Stable gene amplification in the chromosome of Bacillus subtilis

We constructed five different structures, consisting of a genetic marker flanked by directly repeated sequences 2-4 kb long, in the Bacillus subtilis chromosome. When a selective pressure was applied amplification of the marker and one of the repeats was observed in all cases. Amplification was not detected with two markers which were not flanked by the repeated sequences. The maximum amplification level observed with the different structures varied between 5 and 50. The size of the most amplified structure corresponded to 7.5% of the chromosome. Amplification was stable upon growth of cells under non-selective conditions. Each copy of an amplified gene was expressed with equal efficiency. These results indicate that chromosomal gene amplification may be useful for constructing genetically engineered B. subtilis strains.