Transportin regulates nuclear import of CD44.
CD44 is a facultative cell surface proteoglycan that serves as the principal cell surface receptor for hyaluronan (HA). Studies have shown that in addition to participating in numerous signaling pathways, CD44 becomes internalized upon engagement by ligand and that a portion of its intracellular domain can translocate to the nucleus where it is believed to play a functional role in cell proliferation and survival. However, the mechanisms whereby fragments of CD44 enter the nucleus have not been elucidated. Here we show that CD44 interacts with two import receptors of the importin β superfamily, importin β itself and transportin. Inhibition of importin β-dependent transport failed to block CD44 accumulation in the nucleus. By contrast, inhibition of the transportin-dependent pathway abrogated CD44 import. Mutagenesis of the intracellular domain of CD44 revealed that the 20 membrane-proximal residues contain sequences required for transportin-mediated nuclear transport. Our observations provide evidence that CD44 interacts with importin family members and identify the transportin-dependent pathway as the mechanism whereby full-length CD44 enters the nucleus.
Janiszewska
Michalina
M
Division of Experimental Pathology, Institute of Pathology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne CH-1011, Switzerland.
De Vito
Claudio
C
Le Bitoux
Marie-Aude
MA
Fusco
Carlo
C
Stamenkovic
Ivan
I
D021581:Active Transport, Cell Nucleus / Q000502:physiology; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D002470:Cell Survival; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism*; D028884:Karyopherins / Q000235:genetics / Q000378:metabolism*; D016296:Mutagenesis; D017434:Protein Structure, Tertiary; D028961:beta Karyopherins / Q000235:genetics / Q000378:metabolism
C497483:CD44 protein, human; D018960:Hyaluronan Receptors; D028884:Karyopherins; D028961:beta Karyopherins