共查询到20条相似文献,搜索用时 46 毫秒
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Regions of the skeletal muscle dihydropyridine receptor critical for excitation-contraction coupling 总被引:46,自引:0,他引:46
It is thought that in skeletal muscle excitation-contraction (EC) coupling, the release of Ca2+ from the sarcoplasmic reticulum is controlled by the dihydropyridine (DHP) receptor in the transverse tubular membrane, where it serves as the voltage sensor. We have shown previously that injection of an expression plasmid carrying the skeletal muscle DHP receptor complementary DNA restores EC coupling and L-type calcium current that are missing in skeletal muscle myotubes from mutant mice with muscular dysgenesis. This restored coupling resembles normal skeletal muscle EC coupling, which does not require entry of extracellular Ca2+. By contrast, injection into dysgenic myotubes of an expression plasmid carrying the cardiac DHP receptor cDNA produces L-type calcium current and cardiac-type EC coupling, which does require entry of extracellular Ca2+. To identify the regions responsible for this important functional difference between the two structurally similar DHP receptors, we have expressed various chimaeric DHP receptor cDNAs in dysgenic myotubes. The results obtained indicate that the putative cytoplasmic region between repeats II and III of the skeletal muscle DHP receptor is an important determinant of skeletal-type EC coupling. 相似文献
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Shuttling of pre-mRNA binding proteins between nucleus and cytoplasm. 总被引:118,自引:0,他引:118
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A lethal mutation in mice eliminates the slow calcium current in skeletal muscle cells 总被引:17,自引:0,他引:17
Contraction of a vertebrate skeletal muscle fibre is triggered by electrical depolarization of sarcolemmal infoldings termed transverse-tubules (t-tubules), which in turn causes the release of calcium from an internal store, the sarcoplasmic reticulum (SR). The mechanism that links t-tubular depolarization to SR calcium release remains poorly understood. In principle, this link might be provided by the prominent slow calcium current that has been described in skeletal muscle cells of adult frogs and rats. However, blocking this current does not abolish the depolarization-induced contractile responses of frog muscle, and the function of this slow calcium current is unknown. Here we describe measurements of calcium currents in developing skeletal muscle cells of normal rats and mice, and of mice with muscular dysgenesis, a mutation that causes excitation-contraction (E-C) coupling to fail. We find that a slow calcium current is present in skeletal muscle cells of normal animals but absent from skeletal muscle cells of mutant animals. The effect of the mutation is specific to the slow calcium current of skeletal muscle; a fast calcium current is present in developing skeletal muscle cells of both normal and mutant animals, and slow calcium currents are present in cardiac and sensory neurones of mutant animals. We believe this to be the first report of a mutation affecting calcium currents in a multicellular organism. The effects of the mutation raise important questions about the relationship between the slow calcium current and skeletal muscle E-C coupling. 相似文献
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Polyhydroxylated steroids are regulators of body shape and size in higher organisms. In metazoans, intracellular receptors recognize these molecules. Plants, however, perceive steroids at membranes, using the membrane-integral receptor kinase BRASSINOSTEROID INSENSITIVE 1 (BRI1). Here we report the structure of the Arabidopsis thaliana BRI1 ligand-binding domain, determined by X-ray diffraction at 2.5?? resolution. We find a superhelix of 25 twisted leucine-rich repeats (LRRs), an architecture that is strikingly different from the assembly of LRRs in animal Toll-like receptors. A 70-amino-acid island domain between LRRs 21 and 22 folds back into the interior of the superhelix to create a surface pocket for binding the plant hormone brassinolide. Known loss- and gain-of-function mutations map closely to the hormone-binding site. We propose that steroid binding to BRI1 generates a docking platform for a co-receptor that is required for receptor activation. Our findings provide insight into the activation mechanism of this highly expanded family of plant receptors that have essential roles in hormone, developmental and innate immunity signalling. 相似文献
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Membrane depolarization causes many kinds of ion channels to open, a process termed activation. For both Na+ channels and Ca2+ channels, kinetic analysis of current has suggested that during activation the channel undergoes several conformational changes before reaching the open state. Structurally, these channels share a common motif: the central element is a large polypeptide with four repeating units of homology (repeats I-IV), each containing a voltage-sensing region, the S4 segment. This suggests that the distinct conformational transitions inferred from kinetic analysis may be equated with conformational changes of the individual structural repeats. To investigate the molecular basis of channel activation, we constructed complementary DNAs encoding chimaeric Ca2+ channels in which one or more of the four repeats of the skeletal muscle dihydropyridine receptor are replaced by the corresponding repeats derived from the cardiac dihydropyridine receptor. We report here that repeat I determines whether the chimaeric Ca2+ channel shows slow (skeletal muscle-like) or rapid (cardiac-like) activation. 相似文献
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RNA polymerase II C-terminal repeat influences response to transcriptional enhancer signals 总被引:25,自引:0,他引:25
The large subunit of RNA polymerase II contains a highly conserved and essential heptapeptide repeat (Pro-Thr-Ser-Pro-Ser-Tyr-Ser) at its carboxy terminus. Saccharomyces cerevisiae cells are inviable if their RNA polymerase II large subunit genes encode fewer than 10 complete heptapeptide repeats; if they encode 10 to 12 complete repeats cells are temperature-sensitive and cold-sensitive, but 13 or more complete repeats will allow wild-type growth at all temperatures. Cells containing C-terminal domains (CTDs) of 10 to 12 complete repeats are also inositol auxotrophs. The phenotypes associated with these CTD mutations are not a consequence of an instability of the large subunit; rather, they seem to reflect a functional deficiency of the mutant enzyme. We show here that partial deletion mutations in RNA polymerase II CTD affect the ability of the enzyme to respond to signals from upstream activating sequences in a subset of promoters in yeast. The number of heptapeptide repeats required for maximal response to signals from these sequences differs from one upstream activating sequence to another. One of the upstream elements that is sensitive to truncations of the CTD is the 17-base-pair site bound by the GAL4 transactivating factor. 相似文献
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Lim J Crespo-Barreto J Jafar-Nejad P Bowman AB Richman R Hill DE Orr HT Zoghbi HY 《Nature》2008,452(7188):713-718
Spinocerebellar ataxia type 1 (SCA1) is a dominantly inherited neurodegenerative disease caused by expansion of a glutamine-encoding repeat in ataxin 1 (ATXN1). In all known polyglutamine diseases, the glutamine expansion confers toxic functions onto the protein; however, the mechanism by which this occurs remains enigmatic, in light of the fact that the mutant protein apparently maintains interactions with its usual partners. Here we show that the expanded polyglutamine tract differentially affects the function of the host protein in the context of different endogenous protein complexes. Polyglutamine expansion in ATXN1 favours the formation of a particular protein complex containing RBM17, contributing to SCA1 neuropathology by means of a gain-of-function mechanism. Concomitantly, polyglutamine expansion attenuates the formation and function of another protein complex containing ATXN1 and capicua, contributing to SCA1 through a partial loss-of-function mechanism. This model provides mechanistic insight into the molecular pathogenesis of SCA1 as well as other polyglutamine diseases. 相似文献
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DU Guangwei PAN Meihui ZHOU Yan CHENJianhe YAO HuiYUAN Jiangang & QIANG Boqin(National Laboratory of Medical Molecular Biology Institute of Basic Medical Sciences Chinese Academy of Medical Sciences Peking Union Medical College National Centre ofHuman Genome Research Institute Beijing China)Correspondence should be addressed to Yuan Jiangang 《科学通报(英文版)》2000,45(1):343-350
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