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Calreticulin Is a receptor for nuclear export
J M Holaska1, B E Black, D C Love
1Center for Cell Signaling, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908, USA.
The Journal of Cell Biology
|January 10, 2001
Summary
Calreticulin (CRT) mediates nuclear export distinct from Crm1, regulating glucocorticoid receptor (GR) activity. This discovery reveals a new nuclear export pathway for steroid hormone receptors.
Area of Science:
- Cell Biology
- Molecular Biology
- Protein Export
Background:
- Cytosol contains nuclear export activity distinct from Crm1.
- Calreticulin (CRT) was previously localized to the ER lumen.
- CRT is implicated in steroid hormone receptor function.
Purpose of the Study:
- Purify and characterize the novel nuclear export activity.
- Investigate CRT's role in nuclear export of the glucocorticoid receptor (GR).
- Define a new nuclear export pathway.
Main Methods:
- Permeabilized cell assays
- Protein purification and characterization
- Microinjection and transfection assays
- RanGTP binding assays
Main Results:
- Calreticulin (CRT) purified as the novel export activity.
- Cells possess both ER and cytosolic CRT pools.
- CRT mediates PKI and GR nuclear export via a RanGTP-dependent complex.
- GR export utilizes its DNA-binding domain as an NES, independent of leptomycin B.
Conclusions:
- Calreticulin (CRT) mediates a novel nuclear export pathway.
- This pathway regulates glucocorticoid receptor (GR) nuclear export.
- CRT's function extends beyond the ER, impacting transcriptional regulation.