The CD34-related molecule podocalyxin is a potent inducer of microvillus formation
Podocalyxin is a CD34-related transmembrane protein involved in hematopoietic cell homing, kidney morphogenesis, breast cancer progression, and epithelial cell polarization. Although this sialomucin has been shown to block cell adhesion, the mechanisms involved remain enigmatic. It has, however, bee...
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Published in | PloS one Vol. 2; no. 2; p. e237 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Public Library of Science
21.02.2007
Public Library of Science (PLoS) |
Subjects | |
Online Access | Get full text |
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Summary: | Podocalyxin is a CD34-related transmembrane protein involved in hematopoietic cell homing, kidney morphogenesis, breast cancer progression, and epithelial cell polarization. Although this sialomucin has been shown to block cell adhesion, the mechanisms involved remain enigmatic. It has, however, been postulated that the adaptor proteins NHERF-1 and 2 could regulate apical targeting of Podocalyxin by linking it to the actin cytoskeleton.
Here, in contrast, we find that full-length Podocalyxin acts to recruit NHERF-1 to the apical domain. Moreover, we show that ectopic expression of Podocalyxin in epithelial cells leads to microvillus formation along an expanded apical domain that extends laterally to the junctional complexes. Removal of the C-terminal PDZ-binding domain of Podocalyxin abolishes NHERF-1 recruitment but, surprisingly, has no effect on the formation of microvilli. Instead, we find that the extracellular domain and transmembrane region of Podocalyxin are sufficient to direct recruitment of filamentous actin and ezrin to the plasma membrane and induce microvillus formation.
Our data suggest that this single molecule can modulate NHERF localization and, independently, act as a key orchestrator of apical cell morphology, thereby lending mechanistic insights into its multiple roles as a polarity regulator, tumor progression marker, and anti-adhesin. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Conceived and designed the experiments: KM AV JN CR MG. Performed the experiments: AV JN SC MG. Analyzed the data: AV JN MG. Contributed reagents/materials/analysis tools: KM AV JN CR MG. Wrote the paper: KM AV JN CR MG. |
ISSN: | 1932-6203 1932-6203 |
DOI: | 10.1371/journal.pone.0000237 |