Calmodulin activates nuclear protein import: A link between signal transduction and nuclear transport

Calmodulin activates nuclear protein import: A link between signal transduction and nuclear transport

Thomas D. Sweitzer and
John A. Hanover*

Laboratory of Cell Biochemistry and Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0850

Abstract

In addition to the well-characterized GTP-dependent nuclear transport observed in permeabilized cells, we detected a mode of nuclear transport that was GTP-independent at elevated cytoplasmic calcium concentrations. Nuclear transport under these conditions was blocked by calmodulin inhibitors. Recombinant calmodulin restored ATP-dependent nuclear transport in the absence of cytosol. Calmodulin-dependent transport was inhibited by wheat germ agglutinin consistent with transport proceeding through nuclear pores. We propose that release of intracellular calcium stores upon cell activation inhibits GTP-dependent nuclear transport; the elevated cytosolic calcium then acts through calmodulin to stimulate the novel GTP-independent mode of import.

Footnotes

↵ * To whom reprint requests should be addressed.
Gilbert Ashwell, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD
Abbreviations: NLS, nuclear localization sequence; GTPγS, guanosine 5′-o-(3-thiotriphosphate); EC₅₀, effective concentration for 50% of maximal transport.
↵ † Karyopherin-α (4) is used here to denote a functionally analogous class of proteins that includes the NLS-receptor (5), importin-60 (6), importin-α (7), Srp1p (8), Rch1p (6), NPI-1 (9), and NBP60 (10). Karyopherin-β (11, 12) is also known as p97 (13), Kap95p (14), importin-90 (6), and importin-β (7). p10 (11, 12) is also known as NTF2 (15) and pp15 (16).