Conditions required for the inhibitory feedback loop in noradrenergic transmission

Nature ◽  
1981 ◽  
Vol 293 (5827) ◽  
pp. 62-65 ◽  
Author(s):  
D. F. Story ◽  
M. W. McCulloch ◽  
M. J. Rand ◽  
C. A. Standford-Starr
2014 ◽  
Vol 1 ◽  
pp. 636-639
Author(s):  
Fernanda S. Matias ◽  
Pedro V. Carelli ◽  
Claudio R. Mirasso ◽  
Mauro Copelli

2003 ◽  
Vol 170 (3) ◽  
pp. 1304-1312 ◽  
Author(s):  
Wei-Ping Min ◽  
Dejun Zhou ◽  
Thomas E. Ichim ◽  
Gill H. Strejan ◽  
Xiaoping Xia ◽  
...  

2012 ◽  
Vol 47 (1) ◽  
pp. 76-86 ◽  
Author(s):  
Oren Moscovitz ◽  
Peter Tsvetkov ◽  
Nimrod Hazan ◽  
Izhak Michaelevski ◽  
Hodaya Keisar ◽  
...  

1996 ◽  
Vol 315 (1) ◽  
pp. 33-39 ◽  
Author(s):  
Ulrich SEYDEL ◽  
David A. JANS

Nuclear protein import is central to eukaryotic cell function. It is dependent on ATP, temperature and cytosolic factors, and requires specific targeting sequences called nuclear localization signals (NLSs). Nuclear import kinetics was studied in vitro using digitonin-permeabilized cells of the HTC rat hepatoma cell line and a fluorescently labelled β-galactosidase fusion protein carrying amino acids 111–135 of the simian virus 40 large T-antigen (T-ag), including the NLS. Nuclear accumulation was rapid, reaching steady-state after about 80 min at 37 °C (t1/2 at about 17 min). Surprisingly, maximal nuclear concentration was found to be directly proportional to the concentration of the cytosolic extract and of cytoplasmic T-ag protein. Neither preincubation of cells for 1 h at 37 °C before the addition of T-ag protein nor the addition of fresh transport medium after 1 h and continuation of the incubation for another hour affected the maximal nuclear concentration. If cells were allowed to accumulate T-ag protein for 1 h before the addition of fresh transport medium containing different concentrations of T-ag protein and incubated for a further hour, the maximal nuclear concentration did not change unless the concentration of T-ag protein in the second transport mixture exceeded that in the first, in which case the nuclear concentration increased. Nuclear import of T-ag thus appeared (i) to be strictly unidirectional over 2 h at 37 °C and (ii) to be regulated by an inhibitory feedback loop, whereby the cytosolic concentration of protein appears to determine directly the precise end point of nuclear accumulation. This study represents the first characterization of this previously undescribed mechanism of regulation of nuclear protein import.


Development ◽  
1996 ◽  
Vol 122 (11) ◽  
pp. 3363-3370 ◽  
Author(s):  
M. Golembo ◽  
E. Raz ◽  
B.Z. Shilo

The Drosophila EGF receptor (DER) is activated by secreted Spitz to induce different cell fates in the ventral ectoderm. Processing of the precursor transmembrane Spitz to generate the secreted form was shown to be the limiting event, but the cells in which processing takes place and the mechanism that may generate a gradient of secreted Spitz in the ectoderm were not known. The ectodermal defects in single minded (sim) mutant embryos, in which the midline fails to develop, suggested that the midline cells contribute to patterning of the ventral ectoderm. This work shows that the midline provides the site for Spitz expression and processing. The Rhomboid and Star proteins are also expressed and required in the midline. The ectodermal defects of spitz, rho or Star mutant embryos could be rescued by inducing the expression of the respective normal genes only in the midline cells. Rho and Star thus function non-autonomously, and may be required for the production or processing of the Spitz precursor. Secreted Spitz is the only sim-dependent contribution of the midline to patterning the ectoderm, since the ventral defects observed in sim mutant embryos can be overcome by expression of secreted Spitz in the ectoderm. While ectopic expression of secreted Spitz in the ectoderm or mesoderm gave rise to ventralization of the embryo, increased expression of secreted Spitz in the midline did not lead to alterations in ectoderm patterning. A mechanism for adjustment to variable levels of secreted Spitz emanating from the midline may be provided by Argos, which forms an inhibitory feedback loop for DER activation. The production of secreted Spitz in the midline, may provide a stable source for graded DER activation in the ventral ectoderm.


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