44 research outputs found

    An Alpha-Catulin Homologue Controls Neuromuscular Function through Localization of the Dystrophin Complex and BK Channels in Caenorhabditis elegans

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    The large conductance, voltage- and calcium-dependent potassium (BK) channel serves as a major negative feedback regulator of calcium-mediated physiological processes and has been implicated in muscle dysfunction and neurological disorders. In addition to membrane depolarization, activation of the BK channel requires a rise in cytosolic calcium. Localization of the BK channel near calcium channels is therefore critical for its function. In a genetic screen designed to isolate novel regulators of the Caenorhabditis elegans BK channel, SLO-1, we identified ctn-1, which encodes an α-catulin homologue with homology to the cytoskeletal proteins α-catenin and vinculin. ctn-1 mutants resemble slo-1 loss-of-function mutants, as well as mutants with a compromised dystrophin complex. We determined that CTN-1 uses two distinct mechanisms to localize SLO-1 in muscles and neurons. In muscles, CTN-1 utilizes the dystrophin complex to localize SLO-1 channels near L-type calcium channels. In neurons, CTN-1 is involved in localizing SLO-1 to a specific domain independent of the dystrophin complex. Our results demonstrate that CTN-1 ensures the localization of SLO-1 within calcium nanodomains, thereby playing a crucial role in muscles and neurons

    Expression of G protein-coupled receptors and related proteins in HEK293, AtT20, BV2, and N18 cell lines as revealed by microarray analysis

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    <p>Abstract</p> <p>Background</p> <p>G protein coupled receptors (GPCRs) are one of the most widely studied gene superfamilies. Thousands of GPCR research studies have utilized heterologous expression systems such as human embryonic kidney cells (HEK293). Though often treated as 'blank slates', these cell lines nevertheless endogenously express GPCRs and related signaling proteins. The outcome of a given GPCR study can be profoundly influenced by this largely unknown complement of receptors and/or signaling proteins. Little easily accessible information exists that describes the expression profiles of the GPCRs in cell lines. What is accessible is often limited in scope - of the hundreds of GPCRs and related proteins, one is unlikely to find information on expression of more than a dozen proteins in a given cell line. Microarray technology has allowed rapid analysis of mRNA levels of thousands of candidate genes, but though often publicly available, the results can be difficult to efficiently access or even to interpret.</p> <p>Results</p> <p>To bridge this gap, we have used microarrays to measure the mRNA levels of a comprehensive profile of non-chemosensory GPCRs and over a hundred GPCR signaling related gene products in four cell lines frequently used for GPCR research: HEK293, AtT20, BV2, and N18.</p> <p>Conclusions</p> <p>This study provides researchers an easily accessible mRNA profile of the endogenous signaling repertoire that these four cell lines possess. This will assist in choosing the most appropriate cell line for studying GPCRs and related signaling proteins. It also provides a better understanding of the potential interactions between GPCRs and those signaling proteins.</p

    Ockham’s razor for the MET-driven invasive growth linking idiopathic pulmonary fibrosis and cancer

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    Reproduction of Blue-black Grassquits in central Brazil

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    During the reproductive season Blue-black grassquit (Volatinia jacarina) males are found in clusters, wherein they exhibit a distinctive display that consists of repeated, vertical leaps while simultaneously producing a brief vocalization. The main objective of this study was to describe details of the species' reproductive behavior in a "Cerrado" area of central Brazil and compare these data with some studies carried out in other areas. The data obtained concerning different aspects of nesting, laying and hatching were generally similar to those obtained in previous studies in other areas. However, we found that the typical clutch size of two eggs per nest is lower, and egg and nestling mortality rates higher in our area than what has been reported elsewhere. Our results suggest that males differ in time expended with different activities according to their reproductive condition and also provide extensive parental care. We found that display execution rates peak in the early morning and in the late afternoon and are higher in the middle of the breeding season. We also found that there is an inverse relation between the height of the display leap and the height of the perch
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