Domain structure and conformational changes in rat KV2.1 ion channel.

Voltage-gated potassium Kv2.1 channels are widely distributed in the central nervous system, specifically in neuroendocrine and endocrine cells. Their cytoplasmic C-termini are large and carry out many important functions.

Wild-type and Hupki (human p53 knock-in) murine embryonic fibroblasts: p53/ARF pathway disruption in spontaneous escape from senescence.

Research on cell senescence and immortalization of murine embryonic fibroblasts (MEFs) has revealed important clues about genetic control of senescence in humans. To investigate senescence and genetic alterations in the p53 pathway that lead to senescence bypass in culture, we compared the behavior of MEFs from wild-type mice with MEFs from Hupki mice, which harbor a humanized p53 gene. We found that humanizing the p53 gene in mice preserved major features of the MEF senescence/immortalization process.

Roles of surface residues of intracellular domains of heag potassium channels.

Ether-a-go-go potassium channels have large intracellular regions containing 'Per-Ant-Sim' (PAS) and cyclic nucleotide binding (cNBD) domains at the N- and C-termini, respectively. In heag1 and heag2 channels, recent studies have suggested that the N- and C-terminal domains interact, and affect activation properties. Here, we have studied the effect of mutations of residues on the surfaces of PAS and cNBD domains.

Tubulin as a binding partner of the heag2 voltage-gated potassium channel.

The aim of this work was to investigate interactions of the human ether-a-go-go channel heag2 with human brain proteins. For this, we used heag2-GST fusion proteins in pull-down assays with brain proteins and mass spectrometry, as well as coimmunoprecipitation. We identified tubulin and heat shock 70 proteins as binding to intracellular C-terminal regions of the channel.

Molecular rearrangements of the Kv2.1 potassium channel termini associated with voltage gating.

The voltage-gated Kv2.1 channel is composed of four identical subunits folded around the central pore and does not inactivate appreciably during short depolarizing pulses. To study voltage-induced relative molecular rearrangements of the channel, Kv2.

Molecular regions underlying the activation of low- and high-voltage activating calcium channels.

We have studied two aspects of calcium channel activation. First, we investigated the molecular regions that are important in determining differences in activation between low- and high-voltage activated channels. For this, we made chimeras between the low-voltage activating Ca(V)3.

Roles of molecular regions in determining differences between voltage dependence of activation of CaV3.1 and CaV1.2 calcium channels.

Voltage-dependent calcium channels are classified into low voltage-activated and high voltage-activated channels. We have investigated the molecular basis for this difference in voltage dependence of activation by constructing chimeras between a low voltage-activated channel (Ca(V)3.1) and a high voltage-activated channel (Ca(V)1.

The Roles of N- and C-terminal determinants in the activation of the Kv2.1 potassium channel.

The human and rat forms of the Kv2.1 channel have identical amino acids over the membrane-spanning regions and differ only in the N- and C-terminal intracellular regions. Rat Kv2.