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Cellular and Molecular Life Sciences: CMLS

Xingqun Liang, Sylvia M Evans, Yunfu Sun
The sinoatrial node (SAN) is the dominant pacemaker of the heart. Abnormalities in SAN formation and function can cause sinus arrhythmia, including sick sinus syndrome and sudden death. A better understanding of genes and signaling pathways that regulate SAN development and function is essential to develop more effective treatment to sinus arrhythmia, including biological pacemakers. In this review, we briefly summarize the key processes of SAN morphogenesis during development, and focus on the transcriptional network that drives SAN development...
October 21, 2016: Cellular and Molecular Life Sciences: CMLS
Florian Hoss, Juan F Rodriguez-Alcazar, Eicke Latz
The inflammasome adapter ASC links activated inflammasome sensors to the effector molecule pro-caspase-1. Recruitment of pro-caspase-1 to ASC promotes the autocatalytic activation of caspase-1, which leads to the release of pro-inflammatory cytokines, such as IL-1β. Upon triggering of inflammasome sensors, ASC assembles into large helical fibrils that interact with each other serving as a supramolecular signaling platform termed the ASC speck. Alternative splicing, post-translational modifications of ASC, as well as interaction with other proteins can perturb ASC function...
October 19, 2016: Cellular and Molecular Life Sciences: CMLS
A Eraso-Pichot, R Larramona-Arcas, E Vicario-Orri, R Villalonga, L Pardo, E Galea, R Masgrau
Astrocytic excitability relies on cytosolic calcium increases as a key mechanism, whereby astrocytes contribute to synaptic transmission and hence learning and memory. While it is a cornerstone of neurosciences that experiences are remembered, because transmitters activate gene expression in neurons, long-term adaptive astrocyte plasticity has not been described. Here, we investigated whether the transcription factor CREB mediates adaptive plasticity-like phenomena in astrocytes. We found that activation of CREB-dependent transcription reduced the calcium responses induced by ATP, noradrenaline, or endothelin-1...
October 19, 2016: Cellular and Molecular Life Sciences: CMLS
Yusuke Endo, Koutaro Yokote, Toshinori Nakayama
Chronic inflammation associated with obesity plays a major role in the development of metabolic diseases, cancer, and autoimmune diseases. Among Th subsets, Th17 cells are involved in the pathogenesis of autoimmune disorders such as psoriasis, rheumatoid arthritis, inflammatory bowel disease, steroid-resistant asthma, and multiple sclerosis. Accumulating data suggest that reciprocal interactions between the metabolic systems and immune system play pivotal roles in the pathogenesis of obesity-associated diseases...
October 18, 2016: Cellular and Molecular Life Sciences: CMLS
Nicholas J Bradshaw, Mirian A F Hayashi
NDE1 (Nuclear Distribution Element 1, also known as NudE) and NDEL1 (NDE-Like 1, also known as NudEL) are the mammalian homologues of the fungus nudE gene, with important and at least partially overlapping roles for brain development. While a large number of studies describe the various properties and functions of these proteins, many do not directly compare the similarities and differences between NDE1 and NDEL1. Although sharing a high degree structural similarity and multiple common cellular roles, each protein presents several distinct features that justify their parallel but also unique functions...
October 14, 2016: Cellular and Molecular Life Sciences: CMLS
Wanjun Zhu, Xiao-Yan Zhang, Sadie L Marjani, Jialing Zhang, Wengeng Zhang, Shixiu Wu, Xinghua Pan
Single-cell sequencing (SCS) is a fast-growing, exciting field in genomic medicine. It enables the high-resolution study of cellular heterogeneity, and reveals the molecular basis of complicated systems, which facilitates the identification of new biomarkers for diagnosis and for targeting therapies. It also directly promotes the next generation of genomic medicine because of its ultra-high resolution and sensitivity that allows for the non-invasive and early detection of abnormalities, such as aneuploidy, chromosomal translocation, and single-gene disorders...
October 13, 2016: Cellular and Molecular Life Sciences: CMLS
Xin Meng, Jack Clews, Vasileios Kargas, Xiaomeng Wang, Robert C Ford
The cystic fibrosis transmembrane conductance regulator (CFTR) is responsible for the disease cystic fibrosis (CF). It is a membrane protein belonging to the ABC transporter family functioning as a chloride/anion channel in epithelial cells around the body. There are over 1500 mutations that have been characterised as CF-causing; the most common of these, accounting for ~70 % of CF cases, is the deletion of a phenylalanine at position 508. This leads to instability of the nascent protein and the modified structure is recognised and then degraded by the ER quality control mechanism...
October 12, 2016: Cellular and Molecular Life Sciences: CMLS
Susan Schlegel, Pierre Genevaux, Jan-Willem de Gier
Escherichia coli has been widely used for the production of recombinant proteins. To improve protein production yields in E. coli, directed engineering approaches have been commonly used. However, there are only few reported examples of the isolation of E. coli protein production strains using evolutionary approaches. Here, we first give an introduction to bacterial evolution and mutagenesis to set the stage for discussing how so far selection- and screening-based approaches have been used to isolate E. coli protein production strains...
October 11, 2016: Cellular and Molecular Life Sciences: CMLS
Stephanie Chin, Maurita Hung, Christine E Bear
Cystic fibrosis transmembrane conductance regulator (CFTR) channel gating is predominantly regulated by protein kinase A (PKA)-dependent phosphorylation. In addition to regulating CFTR channel activity, PKA phosphorylation is also involved in enhancing CFTR trafficking and mediating conformational changes at the interdomain interfaces of the protein. The major cystic fibrosis (CF)-causing mutation is the deletion of phenylalanine at position 508 (F508del); it causes many defects that affect CFTR trafficking, stability, and gating at the cell surface...
October 8, 2016: Cellular and Molecular Life Sciences: CMLS
Isabelle Callebaut, Brice Hoffmann, Pierre Lehn, Jean-Paul Mornon
The cystic fibrosis transmembrane conductance regulator (CFTR) protein is a member of the ATP-binding cassette (ABC) transporter superfamily that functions as an ATP-gated channel. Considerable progress has been made over the last years in the understanding of the molecular basis of the CFTR functions, as well as dysfunctions causing the common genetic disease cystic fibrosis (CF). This review provides a global overview of the theoretical studies that have been performed so far, especially molecular modelling and molecular dynamics (MD) simulations...
October 7, 2016: Cellular and Molecular Life Sciences: CMLS
Zaffar K Haque, Da-Zhi Wang
In the past decades, the cardiovascular community has laid out the fundamental signaling cascades that become awry in the cardiomyocyte during the process of pathologic cardiac remodeling. These pathways are initiated at the cell membrane and work their way to the nucleus to mediate gene expression. Complexity is multiplied as the cardiomyocyte is subjected to cross talk with other cells as well as a barrage of extracellular stimuli and mechanical stresses. In this review, we summarize the signaling cascades that play key roles in cardiac function and then we proceed to describe emerging concepts of how the cardiomyocyte senses the mechanical and environmental stimuli to transition to the deleterious genetic program that defines pathologic cardiac remodeling...
October 6, 2016: Cellular and Molecular Life Sciences: CMLS
Vinciane Saint-Criq, Michael A Gray
Salt and fluid absorption and secretion are two processes that are fundamental to epithelial function and whole body fluid homeostasis, and as such are tightly regulated in epithelial tissues. The CFTR anion channel plays a major role in regulating both secretion and absorption in a diverse range of epithelial tissues, including the airways, the GI and reproductive tracts, sweat and salivary glands. It is not surprising then that defects in CFTR function are linked to disease, including life-threatening secretory diarrhoeas, such as cholera, as well as the inherited disease, cystic fibrosis (CF), one of the most common life-limiting genetic diseases in Caucasian populations...
October 6, 2016: Cellular and Molecular Life Sciences: CMLS
Kiki Kots, Harold J G Meijer, Klaas Bouwmeester, Francine Govers, Tijs Ketelaar
The oomycete Phytophthora infestans is the cause of late blight in potato and tomato. It is a devastating pathogen and there is an urgent need to design alternative strategies to control the disease. To find novel potential drug targets, we used Lifeact-eGFP expressing P. infestans for high resolution live cell imaging of the actin cytoskeleton in various developmental stages. Previously, we identified actin plaques as structures that are unique for oomycetes. Here we describe two additional novel actin configurations; one associated with plug deposition in germ tubes and the other with appressoria, infection structures formed prior to host cell penetration...
October 6, 2016: Cellular and Molecular Life Sciences: CMLS
Parvin Abraham, Tessy Thomas Maliekal
Research of the past two decades has proved the relevance of single cell biology in basic research and translational medicine. Successful detection and isolation of specific subsets is the key to understand their functional heterogeneity. Antibodies are conventionally used for this purpose, but their relevance in certain contexts is limited. In this review, we discuss some of these contexts, posing bottle neck for different fields of biology including biomedical research. With the advancement of chemistry, several methods have been introduced to overcome these problems...
October 6, 2016: Cellular and Molecular Life Sciences: CMLS
Carlo Castellani, Baroukh M Assael
Cystic fibrosis (CF), a monogenic disease caused by mutations in the CFTR gene on chromosome 7, is complex and greatly variable in clinical expression. Airways, pancreas, male genital system, intestine, liver, bone, and kidney are involved. The lack of CFTR or its impaired function causes fat malabsorption and chronic pulmonary infections leading to bronchiectasis and progressive lung damage. Previously considered lethal in infancy and childhood, CF has now attained median survivals of 50 years of age, mainly thanks to the early diagnosis through neonatal screening, recognition of mild forms, and an aggressive therapeutic attitude...
October 5, 2016: Cellular and Molecular Life Sciences: CMLS
Olga Zegarra-Moran, Luis J V Galietta
CFTR protein is an ion channel regulated by cAMP-dependent phosphorylation and expressed in many types of epithelial cells. CFTR-mediated chloride and bicarbonate secretion play an important role in the respiratory and gastrointestinal systems. Pharmacological modulators of CFTR represent promising drugs for a variety of diseases. In particular, correctors and potentiators may restore the activity of CFTR in cystic fibrosis patients. Potentiators are also potentially useful to improve mucociliary clearance in patients with chronic obstructive pulmonary disease...
October 4, 2016: Cellular and Molecular Life Sciences: CMLS
Oscar Moran
No abstract text is available yet for this article.
October 4, 2016: Cellular and Molecular Life Sciences: CMLS
Carlos M Farinha, Sara Canato
CFTR biogenesis starts with its co-translational insertion into the membrane of endoplasmic reticulum and folding of the cytosolic domains, towards the acquisition of a fully folded compact native structure. Efficiency of this process is assessed by the ER quality control system that allows the exit of folded proteins but targets unfolded/misfolded CFTR to degradation. If allowed to leave the ER, CFTR is modified at the Golgi and reaches the post-Golgi compartments to be delivered to the plasma membrane where it functions as a cAMP- and phosphorylation-regulated chloride/bicarbonate channel...
October 3, 2016: Cellular and Molecular Life Sciences: CMLS
Georgia Dalagiorgou, Christina Piperi, Christos Adamopoulos, Urania Georgopoulou, Antonios N Gargalionis, Anastasia Spyropoulou, Ilianna Zoi, Marjan Nokhbehsaim, Anna Damanaki, James Deschner, Efthimia K Basdra, Athanasios G Papavassiliou
Polycystin-1 (PC1) has been proposed as a chief mechanosensing molecule implicated in skeletogenesis and bone remodeling. Mechanotransduction via PC1 involves proteolytic cleavage of its cytoplasmic tail (CT) and interaction with intracellular pathways and transcription factors to regulate cell function. Here we demonstrate the interaction of PC1-CT with JAK2/STAT3 signaling axis in mechanically stimulated human osteoblastic cells, leading to transcriptional induction of Runx2 gene, a master regulator of osteoblastic differentiation...
October 3, 2016: Cellular and Molecular Life Sciences: CMLS
Paul Linsdell
The main function of the cystic fibrosis transmembrane conductance regulator (CFTR) is as an ion channel for the movement of small anions across epithelial cell membranes. As an ion channel, CFTR must form a continuous pathway across the cell membrane-referred to as the channel pore-for the rapid electrodiffusional movement of ions. This review summarizes our current understanding of the architecture of the channel pore, as defined by electrophysiological analysis and molecular modeling studies. This includes consideration of the characteristic functional properties of the pore, definition of the overall shape of the entire extent of the pore, and discussion of how the molecular structure of distinct regions of the pore might control different facets of pore function...
October 3, 2016: Cellular and Molecular Life Sciences: CMLS
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