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Elizabeth Storer Scholl Antonella Pirone Daniel H Cox R Keith Duncan Michele H Jacob 《Channels (Austin, Tex.)》2014,8(1):62-75
Small conductance Ca2+-sensitive potassium (SK2) channels are voltage-independent, Ca2+-activated ion channels that conduct potassium cations and thereby modulate the intrinsic excitability and synaptic transmission of neurons and sensory hair cells. In the cochlea, SK2 channels are functionally coupled to the highly Ca2+ permeant α9/10-nicotinic acetylcholine receptors (nAChRs) at olivocochlear postsynaptic sites. SK2 activation leads to outer hair cell hyperpolarization and frequency-selective suppression of afferent sound transmission. These inhibitory responses are essential for normal regulation of sound sensitivity, frequency selectivity, and suppression of background noise. However, little is known about the molecular interactions of these key functional channels. Here we show that SK2 channels co-precipitate with α9/10-nAChRs and with the actin-binding protein α-actinin-1. SK2 alternative splicing, resulting in a 3 amino acid insertion in the intracellular 3′ terminus, modulates these interactions. Further, relative abundance of the SK2 splice variants changes during developmental stages of synapse maturation in both the avian cochlea and the mammalian forebrain. Using heterologous cell expression to separately study the 2 distinct isoforms, we show that the variants differ in protein interactions and surface expression levels, and that Ca2+ and Ca2+-bound calmodulin differentially regulate their protein interactions. Our findings suggest that the SK2 isoforms may be distinctly modulated by activity-induced Ca2+ influx. Alternative splicing of SK2 may serve as a novel mechanism to differentially regulate the maturation and function of olivocochlear and neuronal synapses. 相似文献
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Methanobacterium thermoautotrophicum, an archaebacterium, possesses the first and last enzymes of the diaminopimelic acid pathway for lysine biosynthesis, dihydrodipicolinate synthase, and diaminopimelate decarboxylase. It does not have saccharopine dehydrogenase, the last enzyme of the aminoadipate pathway for lysine biosynthesis. The dihydrodipicolinate synthase is inhibited but not repressed by lysine. We conclude that this microbe uses the diaminopimelate pathway for synthesis of lysine.Deceased. 相似文献
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Injection of manganese into the rat corpus striatum causes a rapid fall in the biopterin and dopamine (DA) content ipsilateral to the lesion. Two weeks after the lesion both biopterin and DA are partially recovered. Controls, injected with saline or magnesium, do not show alterations in their DA or cofactor levels. It is proposed that the fall in DA levels results from a rapid displacement of the amine from its storage sites by manganese followed by a decrease in the rate of DA synthesis causes by the drop in cofactor levels. 相似文献
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Keith G. Danielson Janice E. Knepper Frances S. Kittrell Janet S. Butel Daniel Medina Elisa M. Durban 《In vitro cellular & developmental biology. Plant》1989,25(6):535-543
Summary Clonal populations were isolated from the mouse mammary cell line, COMMA-D, by transfection with a dominant-selectable gene,
pSV2Neo, which confers resistance to the antibiotic, G418. Seven of twenty-four clones isolated retained the ability of the
parental line to repopulate cleared mammary fat pads in vivo as ductal-alveolar hyperplasias. Two sublines designated CDNR2
and CDNR4 retained hyperplastic growth potential after multiple passages in vitro with low incidence of tumor formation. A
third subpopulation, CDNR1, contained a single integration site for the pSV2Neo plasmid indicating a bonafide clonal origin
for this subline. CDNR1 cells displayed heterogeneous growth phenotypes in vivo including hyperplasia, adenocarcinoma, and
bone formation. Functional differentiation of CDNR1 cells organized as alveolarlike structures in vivo or on floating collagen
gels in vitro was observed as determined by immunoperoxidase staining for the milk-specific protein, casein. Overall, the
results indicate that a subset of cells from the COMMA-D cell line may be functionally analogous to stem cells existing in
the mammary gland.
Supported by NCI research grants CA-38650, CA-33369, CA-39017, and CA-25215. 相似文献
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David G. Reid David M. Doddrell Dudley H. Williams Keith R. Fox 《Biochimica et Biophysica Acta (BBA)/General Subjects》1984,798(1):111-114
Uniformly 15N-labelled triostin A and echinomycin have been prepared by growing the producing organisms on enriched media and their 15N nuclear magnetic resonance spectra partially assigned by a combination of nuclear Overhauser effect and scalar coupling constant measurements. Selective feeding experiments using unlabelled L-tryptophan-supplemented media have shown that N-1 and N-4 of the quinoxaline rings have their origins in the indole and amino groups of tryptophan, respectively. 相似文献