1,721,083 research outputs found
Direct interaction of gbetagamma with a C-terminal gbetagamma-binding domain of the Ca2+ channel alpha1 subunit is responsible for channel inhibition by G protein-coupled receptors
No full textSeveral classes of voltage-gated Ca2+ channels (VGCCs) are inhibited by G proteins activated by receptors for neurotransmitters and neuromodulatory peptides, Evidence has accumulated to indicate that for non-L-type Ca2+ channels the executing arm of the activated G protein is its beta gamma dimer (G beta gamma). We report below the existence of two G beta gamma-binding sites on the A-, B-, and E-type alpha(1) subunits that form non-L-type Ca2+ channels. One, reported previously, is in loop 1 connecting transmembrane domains I and Il, The second is located approximately in the middle of the ca, 600-aa-long C-terminal tails, Both G beta gamma-binding regions also bind the Ca2+ channel beta subunit (CC beta), which, when overexpressed, interferes with inhibition by activated G proteins, Replacement in alpha(1E) Of loop 1 with that of the G protein-insensitive and G beta gamma-binding-negative loop 1 of alpha(1C) did not abolish inhibition by G proteins, but the exchange of the alpha(1E) C terminus with that of alpha(1C) did, This and properties of alpha(1E) C-terminal truncations indicated that the G beta gamma-binding site mediating the inhibition of Ca2+ channel activity is the one in the C terminus, Binding of G beta gamma to this site mas inhibited by an alpha(1)-binding domain of CC beta, thus providing an explanation for the functional antagonism existing between CC beta and G protein inhibition. The data do not support proposals that G beta gamma inhibits alpha(1) function by interacting with the site located in the loop I-II linker, These results define the molecular mechanism by which presynaptic G protein-coupled receptors inhibit neurotransmission
Structures and functions of calcium channel beta subunits
No full textCalcium channel beta subunits have profound effects on how alpha(1) subunits perform. In this article we summarize our present knowledge of the primary structures of beta subunits as deduced from cDNAs and illustrate their different properties. Upon co-expression with alpha(1) subunits, the effects of beta subunits vary somewhat between L-type and non-L-type channels mostly because the two types of channels have different responses to voltage which are affected by beta subunits, such as lone-lasting prepulse facilitation of alpha(1C) (absent in alpha(1E)) and inhibition by G protein beta gamma dimer of alpha(1E), absent in alpha(1C). One beta subunit, a brain beta 2a splice variant that is palmitoylated, has several effects not seen with any of the others, and these are due to palmitoylation. We also illustrate the finding that functional expression of alpha(1) in oocytes requires a beta subunit even if the final channel shows no evidence for its presence. We propose two structural models for Ca2+ channels to account for "alpha(1) alone" channels seen in cells with limited beta subunit expression. In one model, beta dissociates from the mature alpha(1) after proper folding and membrane insertion. Regulated channels seen upon co-expression of high levels of beta would then have subunit composition alpha(1)beta In the other model, the "chaperoning" beta remains associated with the mature channel and "alpha(1) alone" channels would in fact be alpha(1)beta channels. Upon co-expression of high levels of beta the regulated channels would have composition [alpha(1)beta]beta
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Dual activation of the cardiac Ca2+ channel alpha 1C-subunit and its modulation by the beta-subunit.
No full textA MONOCLONAL-ANTIBODY TO THE ALPHA-SUBUNIT OF GK BLOCKS MUSCARINIC ACTIVATION OF ATRIAL K+ CHANNELS
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Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Unique regulatory properties of the type 2a Ca2+ channel beta subunit caused by palmitoylation
No full textbeta subunits of voltage-gated Ca2+ channels are encoded in four genes and display additional molecular diversity because of alternative splicing. At the functional level, all forms are very-similar except for beta 2a, which differs in that it does not support prepulse facilitation of alpha(1C) Ca2+ channels, inhibits voltage-induced inactivation of neuronal alpha(1E) Ca2+ channels, and is more effective in blocking inhibition of alpha(1E) channels by G protein-coupled receptors. We show that the distinguishing properties of beta 2a, rather than interaction with a distinct site of alpha(1), are because of the recently described palmitoylation of cysteines in positions three and four, which also occurs in the Xenopus oocyte. Essentially, all of the distinguishing features of beta 2a were lost in a mutant that could not be palmitoylated [beta 2a(Cys(3,4)Ser)]. Because protein palmitoylation is a dynamic process, these findings point to the possibility that regulation of palmitoylation may contribute to activity-dependent neuronal and synaptic plasticity. Evidence is presented that there may exist as many as three beta 2 splice variants differing only in their N-termini
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