HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: 2005-0426v1 24/5/1150    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints/Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tan, P. C. Articles by McNagny, K. M. Search for Related Content PubMed PubMed Citation Articles by Tan, P. C. Articles by McNagny, K. M.

STEM CELL GENETICS AND GENOMICS

Na⁺/H⁺ Exchanger Regulatory Factor-1 Is a Hematopoietic Ligand for a Subset of the CD34 Family of Stem Cell Surface Proteins

^a The Biomedical Research Centre and
^b Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, British Columbia, Canada

Key Words. Hematopoiesis • Adhesion • Differentiation • Stem cells • CD34 • Podocalyxin • Endoglycan • Sialomucin • Na⁺/H⁺ exchanger regulatory factor-1 • Na⁺/H⁺ exchanger regulatory factor-2

Correspondence: Kelly M. McNagny, Ph.D., The Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada. Telephone: +1-604-822-7810; Fax: +1-604-822-7815; e-mail: kelly{at}brc.ubc.ca

Received August 30, 2005; accepted for publication January 6, 2006.
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 antiadhesion 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 c-kit⁺ /lineage marker^– /Sca-1⁺ cells, which are known to express podocalyxin and have long-term repopulating abilities. Finally, we show that these proteins relocalize and colocalize 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.

This article has been cited by other articles:

				J. S. Nielsen and K. M. McNagny Novel functions of the CD34 family J. Cell Sci., November 15, 2008; 121(22): 3683 - 3692. [Abstract] [Full Text] [PDF]