PubMed Health⌕ Search

Biomedical subjects

Bryce M Paschal

Publications and source records attributed to Bryce M Paschal.

4 recordsLinked to original sources
PubMed2002

Regulation of nuclear import and export by the GTPase Ran.

This review focuses on the control of nuclear import and export pathways by the small GTPase Ran. Transport of signal-containing cargo substrates is mediated by receptors that bind to the cargo proteins and RNAs and deliver them to the appropriate cellular compartment. Ran is an evolutionarily conserved member of the Ras superfamily that regulates all receptor-mediated transport between the nucleus and the cytoplasm. We describe the identification and characterization of the RanGTPase and its binding partners: the guanine nucleotide exchange factor, RanGEF; the GTPase activating protein, RanGAP; the soluble import and export receptors; Ran-binding domain-(RBD) containing proteins; and NTF2 and related factors.

Active Transport, Cell Nucleus↗
PubMed2002

Ca2+-dependent nuclear export mediated by calreticulin.

We have characterized a pathway for nuclear export of the glucocorticoid receptor (GR) in mammalian cells. This pathway involves the Ca2+ -binding protein calreticulin (CRT), which directly contacts the DNA binding domain (DBD) of GR and facilitates its delivery from the nucleus to the cytoplasm. In the present study, we investigated the role of Ca2+ in CRT-dependent export of GR. We found that removal of Ca2+ from CRT inhibits its capacity to stimulate the nuclear export of GR in digitonin-permeabilized cells and that the inhibition is due to the failure of Ca2+-free CRT to bind the DBD. These effects are reversible, since DBD binding and nuclear export can be restored by Ca2+ addition. Depletion of intracellular Ca2+ inhibits GR export in intact cells under conditions that do not inhibit other nuclear transport pathways, suggesting that there is a Ca2+ requirement for GR export in vivo. We also found that the Ran GTPase is not required for GR export. These data show that the nuclear export pathway used by steroid hormone receptors such as GR is distinct from the Crm1 pathway. We suggest that signaling events that increase Ca2+ could positively regulate CRT and inhibit GR function through nuclear export.

Active Transport, Cell Nucleus↗