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11.
Cloning, sequencing and expression of cDNA for a novel subunit of acetylcholine receptor from calf muscle 总被引:5,自引:0,他引:5
T Takai M Noda M Mishina S Shimizu Y Furutani T Kayano T Ikeda T Kubo H Takahashi T Takahashi 《Nature》1985,315(6022):761-764
The nicotinic acetylcholine receptor (AChR) from fish electric organ has a subunit structure of alpha 2 beta gamma delta, and this is thought to be also the case for the mammalian skeletal muscle AChR. By cloning and sequencing the complementary or genomic DNAs, we have previously elucidated the primary structures of all four subunits of the Torpedo californica electroplax and calf muscle AChR and of the alpha- and gamma-subunits of the human muscle AChR; the primary structures of the gamma-subunit of the T. californica AChR and the alpha-subunit of the Torpedo marmorata AChR have also been deduced elsewhere. We have now cloned DNA complementary to the calf muscle messenger RNA encoding a novel polypeptide (the epsilon-subunit) whose deduced amino-acid sequence has features characteristic of the AChR subunits and which shows higher sequence homology with the gamma-subunit than with the other subunits. cDNA expression studies indicate that the calf epsilon-subunit, as well as the calf gamma-subunit, can replace the Torpedo gamma-subunit to form the functional receptor in combination with the Torpedo alpha-, beta- and delta-subunits. 相似文献
12.
Structure-function relationships of the sodium channel expressed in Xenopus oocytes have been investigated by the combined use of site-directed mutagenesis and patch-clamp recording. This study provides evidence that the positive charges in segment S4 are involved in the voltage-sensing mechanism for activation of the channel and that the region between repeats III and IV is important for its inactivation. 相似文献
13.
Nogi T Yasui N Mihara E Matsunaga Y Noda M Yamashita N Toyofuku T Uchiyama S Goshima Y Kumanogoh A Takagi J 《Nature》2010,467(7319):1123-1127
Semaphorins and their receptor plexins constitute a pleiotropic cell-signalling system that is used in a wide variety of biological processes, and both protein families have been implicated in numerous human diseases. The binding of soluble or membrane-anchored semaphorins to the membrane-distal region of the plexin ectodomain activates plexin's intrinsic GTPase-activating protein (GAP) at the cytoplasmic region, ultimately modulating cellular adhesion behaviour. However, the structural mechanism underlying the receptor activation remains largely unknown. Here we report the crystal structures of the semaphorin 6A (Sema6A) receptor-binding fragment and the plexin A2 (PlxnA2) ligand-binding fragment in both their pre-signalling (that is, before binding) and signalling (after complex formation) states. Before binding, the Sema6A ectodomain was in the expected 'face-to-face' homodimer arrangement, similar to that adopted by Sema3A and Sema4D, whereas PlxnA2 was in an unexpected 'head-on' homodimer arrangement. In contrast, the structure of the Sema6A-PlxnA2 signalling complex revealed a 2:2 heterotetramer in which the two PlxnA2 monomers dissociated from one another and docked onto the top face of the Sema6A homodimer using the same interface as the head-on homodimer, indicating that plexins undergo 'partner exchange'. Cell-based activity measurements using mutant ligands/receptors confirmed that the Sema6A face-to-face dimer arrangement is physiologically relevant and is maintained throughout signalling events. Thus, homodimer-to-heterodimer transitions of cell-surface plexin that result in a specific orientation of its molecular axis relative to the membrane may constitute the structural mechanism by which the ligand-binding 'signal' is transmitted to the cytoplasmic region, inducing GAP domain rearrangements and activation. 相似文献
14.
Primary structure of alpha-subunit precursor of Torpedo californica acetylcholine receptor deduced from cDNA sequence 总被引:65,自引:0,他引:65
M Noda H Takahashi T Tanabe M Toyosato Y Furutani T Hirose M Asai S Inayama T Miyata S Numa 《Nature》1982,299(5886):793-797
DNA sequences complementary to the Torpedo californica electroplax mRNA coding for the alpha-subunit precursor of the acetylcholine receptor were cloned. The nucleotide sequence of the cloned cDNA indicates that the precursor consists of 461 amino acids including a prepeptide of 24 amino acids. Possible sites for acetylcholine binding and antigenic determinants on the alpha-subunit molecule are discussed. 相似文献
15.
Molecular distinction between fetal and adult forms of muscle acetylcholine receptor 总被引:71,自引:0,他引:71
M Mishina T Takai K Imoto M Noda T Takahashi S Numa C Methfessel B Sakmann 《Nature》1986,321(6068):406-411
Distinct classes of acetylcholine receptor channels are formed when Xenopus oocytes are injected with combinations of the bovine alpha-, beta-, gamma- and delta- or the alpha-, beta-, gamma- and epsilon-subunit-specific messenger RNAs. The conductance and gating properties of the two classes of channels, in conjunction with the developmental changes in the muscular contents of the mRNAs, suggest that replacement of the gamma-subunit by the epsilon-subunit is responsible for the functional alteration of the receptor during muscle development. 相似文献
16.
Compact lasers that can produce a range of beam patterns are important for progress in several areas, including the improvement of optical tweezers, ultra-high-density optical memory and microfluidics. Here we engineer photonic crystals to generate semiconductor lasers that produce a range of beam patterns while maintaining stable single-mode oscillation. Our results could contribute to the realization of compact lasers that are capable of producing diverse beam patterns on demand. 相似文献
17.
Hozumi S Maeda R Taniguchi K Kanai M Shirakabe S Sasamura T Spéder P Noselli S Aigaki T Murakami R Matsuno K 《Nature》2006,440(7085):798-802
The internal organs of animals often have left-right asymmetry. Although the formation of the anterior-posterior and dorsal-ventral axes in Drosophila is well understood, left-right asymmetry has not been extensively studied. Here we find that the handedness of the embryonic gut and the adult gut and testes is reversed (not randomized) in viable and fertile homozygous Myo31DF mutants. Myo31DF encodes an unconventional myosin, Drosophila MyoIA (also referred to as MyoID in mammals; refs 3, 4), and is the first actin-based motor protein to be implicated in left-right patterning. We find that Myo31DF is required in the hindgut epithelium for normal embryonic handedness. Disruption of actin filaments in the hindgut epithelium randomizes the handedness of the embryonic gut, suggesting that Myo31DF function requires the actin cytoskeleton. Consistent with this, we find that Myo31DF colocalizes with the cytoskeleton. Overexpression of Myo61F, another myosin I (ref. 4), reverses the handedness of the embryonic gut, and its knockdown also causes a left-right patterning defect. These two unconventional myosin I proteins may have antagonistic functions in left-right patterning. We suggest that the actin cytoskeleton and myosin I proteins may be crucial for generating left-right asymmetry in invertebrates. 相似文献
18.
Jin D Liu HX Hirai H Torashima T Nagai T Lopatina O Shnayder NA Yamada K Noda M Seike T Fujita K Takasawa S Yokoyama S Koizumi K Shiraishi Y Tanaka S Hashii M Yoshihara T Higashida K Islam MS Yamada N Hayashi K Noguchi N Kato I Okamoto H Matsushima A Salmina A Munesue T Shimizu N Mochida S Asano M Higashida H 《Nature》2007,446(7131):41-45
CD38, a transmembrane glycoprotein with ADP-ribosyl cyclase activity, catalyses the formation of Ca2+ signalling molecules, but its role in the neuroendocrine system is unknown. Here we show that adult CD38 knockout (CD38-/-) female and male mice show marked defects in maternal nurturing and social behaviour, respectively, with higher locomotor activity. Consistently, the plasma level of oxytocin (OT), but not vasopressin, was strongly decreased in CD38-/- mice. Replacement of OT by subcutaneous injection or lentiviral-vector-mediated delivery of human CD38 in the hypothalamus rescued social memory and maternal care in CD38-/- mice. Depolarization-induced OT secretion and Ca2+ elevation in oxytocinergic neurohypophysial axon terminals were disrupted in CD38-/- mice; this was mimicked by CD38 metabolite antagonists in CD38+/+ mice. These results reveal that CD38 has a key role in neuropeptide release, thereby critically regulating maternal and social behaviours, and may be an element in neurodevelopmental disorders. 相似文献
19.
20.
Elefteriou F Ahn JD Takeda S Starbuck M Yang X Liu X Kondo H Richards WG Bannon TW Noda M Clement K Vaisse C Karsenty G 《Nature》2005,434(7032):514-520