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CD82 Regulation of Hematopoietic Stem/Progenitor Cell - Niche Adhesion


Please use this identifier to cite or link to this item: http://hdl.handle.net/1928/20974

CD82 Regulation of Hematopoietic Stem/Progenitor Cell - Niche Adhesion

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dc.contributor.author Cotter, Maura L.
dc.date.accessioned 2012-08-27T20:39:09Z
dc.date.issued 2012-08-27
dc.date.submitted July 2012
dc.identifier.uri http://hdl.handle.net/1928/20974
dc.description.abstract The spatial organization and dynamics of proteins and lipids within the cell membrane is important for the regulation of cell signaling, adhesion, and cell communication. Within the bone marrow niche, communication between hematopoietic stem/progenitor cells (HSPCs) and niche cells is essential for regulating their proliferation, differentiation, and survival. Our previous work has ascertained that HSPCs utilize a polarized domain on the plasma membrane that serves as the contact site with osteoblasts, which are important members of the bone marrow niche. Using human primary CD34+ stem/progenitor cells and the progenitor-like KG1a cell line, we found this domain to be enriched in the specific tetraspanin proteins, CD63, CD81, and CD82. Tetraspanins are multi-spanning membrane proteins that act as scaffolds for the organization of membrane domains important for regulating adhesion and signaling. CD82 is of particular interest, as it is highly expressed on HSPCs and downregulated during HSPC differentiation. Our characterization of CD82 function using CD82-blocking antibodies revealed a significant decrease in adhesion of HSPCs to niche cells as well as in the in vivo homing and engraftment capabilities of these cells. To determine the molecular mechanisms of CD82’s role in adhesion, we have generated CD82 overexpression and knockdown cell lines using the KG1a background. Our data indicate that the level of CD82 expression positively correlates with the extent of adhesion to fibronectin and osteoblasts but has no effect on binding to collagen I or laminin. The increase in adhesion we observed with CD82 overexpression was inhibited by the VLA-4-specific peptide, LDV, indicating a potential role for the VLA-4 (α4β1) integrin. Investigations into potential CD82-mediated mechanisms of VLA-4 regulation have revealed that CD82 regulates both the expression and avidity of VLA-4 but does not regulate its affinity. Taken together, the VLA-4 expression and avidity changes could account for the observed adhesion changes with differing CD82 expression levels. Finally, assessment of CD82 palmitoylation using KG1a CD82 palmitoylation mutant cells revealed that palmitoylation may be required for the CD82-induced changes in adhesion. en_US
dc.language.iso en_US en_US
dc.subject Hematopoietic Stem Cell en_US
dc.subject Bone Marrow en_US
dc.subject Niche en_US
dc.subject Osteoblast en_US
dc.subject Fibronectin en_US
dc.subject Adhesion en_US
dc.subject Integrin en_US
dc.subject α4β1 en_US
dc.subject VLA-4 en_US
dc.subject Tetraspanin en_US
dc.subject CD82 en_US
dc.subject.lcsh Cellular signal transduction.
dc.subject.lcsh Cell membranes.
dc.subject.lcsh Hematopoietic stem cells.
dc.subject.lcsh Osteoblasts.
dc.subject.lcsh Cell adhesion.
dc.subject.lcsh Integrins.
dc.subject.lcsh Fibronectins.
dc.title CD82 Regulation of Hematopoietic Stem/Progenitor Cell - Niche Adhesion en_US
dc.type Thesis en_US
dc.description.degree Biomedical Sciences en_US
dc.description.level Masters en_US
dc.description.department University of New Mexico. Biomedical Sciences Graduate Program en_US
dc.description.advisor Gillette, Jennifer
dc.description.committee-member Buranda, Tione
dc.description.committee-member Cannon, Judy
dc.description.committee-member Hartley, Rebecca
emb.embargo.terms 2014-08-31
emb.embargo.lift 2014-08-31

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