NHERF-1 is an Hematopoietic Ligand for a Subset of the CD34 Family of Stem Cell Surface Proteins

¹ The Biomedical Research Centre, University of British Columbia, Vancouver, Canada
² Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, Canada

^* To whom correspondence should be addressed. E-mail: kelly{at}brc.ubc.ca.

	Abstract

CD34 and its relatives, Podocalyxin and Endoglycan, comprise a family of surface sialomucins expressed by hematopoietic stem/progenitor cells, and vascular endothelia. Recent data suggest that they serve as either pro- or anti-adhesion molecules depending on their cellular context and their post-translational modifications. In addition, their ability to function as blockers of adhesion may be further regulated by their subcellular localization in membrane microdomains via activation-dependent linkage with the actin cytoskeleton. To gain further insights into the function and regulation of CD34-type molecules we sought to identify the intracellular ligands that govern their localization. Using both genetic and biochemical approaches we have identified the Na+/H+ exchanger regulatory factor-1, NHERF-1, as a selective ligand for Podocalyxin and Endoglycan but not for the closely related CD34. Furthermore, we show that NHERF-1 is expressed by all KLS cells, which, are known to express Podocalyxin and have long-term repopulating abilities. Finally, we show that these proteins re-localize and co-localize in response to cytokine signaling. The results suggest that this cytosolic adaptor protein may be important for mobilization of CD34- type proteins in the plasma membrane and may thereby regulate their ability to block or enhance hematopoietic cell adhesion.

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