85 research outputs found
Ion channels in the nuclear envelope
No full textCELL nuclei are capable of partitioning a wide variety of molecules from the cytosol, including macromolecules such as proteins1-11 and RNA12-14, and smaller peptides9,14-16, amino acids17, sugars18,19 and Na+ and K+ ions20,21, all of which can be accumulated in or excluded from the nuclear domain. There are two mechanisms behind this compartmentalization: selective retention of freely diffusible molecules, and selective entry through the nuclear envelope. It is generally accepted that the nuclear envelope restricts only the larger molecules22-24. Here we apply the patch-clamp technique to isolated murine pronuclei25 and show that the nuclear envelope contains K+-selective channels which have multiple conductance states, the maximal conductance being 200 pS. These channels, which contribute to the nuclear membrane potential26, may be important in balancing the charge carried by the movement of macromolecules in and out of the nucleus
Why scientists cover up fraud
No full textSir John Madox (Nature 350, 269; 1991) asks why a scientist like David Baltimore should have so vigorously defended what has now proved to be a false position. Philip Weiss raises an even broader issue in his article on scientific fraud (Ney York Times Magazine 29 October 1989), namely why "no one who was equipped to wanted to get to the truth of the matter...
Ca2+/Calmodulin-dependent Protein Kinase II Anchoring to L-type Ca2+ Channels by the Beta Subunits Enhances Regulatory Phosphorylation at Thr498
No full textCa2+/Calmodulin-dependent Protein Kinase II Anchoring to L-type Ca2+ Channels by the Beta Subunits Enhances Regulatory Phosphorylation at Thr498
No full textCalcium/calmodulin-dependent kinase II (CaMKII) facilitates L-type calcium channel (LTCC) activity physiologically, but may exacerbate LTCC-dependent pathophysiology. We previously showed that CaMKII forms stable complexes with voltage-gated calcium channel (VGCC) β1b or β2a subunits, but not with the β3 or β4 subunits (Grueter et al. 2008). CaMKII-dependent facilitation of CaV1.2 LTCCs requires Thr498 phosphorylation in the β2a subunit (Grueter et al. 2006), but the relationship of this modulation to CaMKII interactions with LTCC subunits is unknown. Here we show that CaMKII co-immunoprecipitates with forebrain LTCCs that contain CaV1.2α1 and β1 or β2 subunits, but is not detected in LTCC complexes containing β4 subunits. CaMKIIα can be specifically tethered to the I/II linker of CaV1.2 α1 subunits in vitro by the β1b or β2a subunits. Efficient targeting of CaMKIIα to the full-length CaV1.2α1 subunit in transfected HEK293 cells requires CaMKII binding to the β2a subunit. Moreover, disruption of CaMKII binding substantially reduced phosphorylation of β2a at Thr498 within the LTCC complex, without altering overall phosphorylation of CaV1.2α1 and β subunits. These findings demonstrate a biochemical mechanism underlying LTCC facilitation by CaMKII
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