The CD34-related molecule podocalyxin is a potent inducer of microvillus formation.

Abstract

BACKGROUND:

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.

PRINCIPAL FINDINGS:

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.

CONCLUSIONS/SIGNIFICANCE:

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.

• Authors: Julie S Nielsen, Marcia L Graves, Shierley Chelliah, A Wayne Vogl, Calvin D Roskelley, Kelly M McNagny
• Journal: PloS one (PLoS One) Vol. 2 Issue 2 Pg. e237 (Feb 21 2007) ISSN: 1932-6203 [Electronic] United States
• PMID: 17311105 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Actins
• Cytoskeletal Proteins
• Peptide Fragments
• Phosphoproteins
• Recombinant Fusion Proteins
• Sialoglycoproteins
• Sodium-Hydrogen Exchangers
• ezrin
• podocalyxin
• sodium-hydrogen exchanger regulatory factor

Topics

• Actins (physiology)
• Amino Acid Sequence
• Animals
• Cell Line (ultrastructure)
• Cell Polarity
• Chickens
• Cytoskeletal Proteins (physiology)
• Dogs
• Epithelial Cells (ultrastructure)
• Female
• Humans
• Mice
• Microvilli (physiology)
• Molecular Sequence Data
• Peptide Fragments (metabolism)
• Phosphoproteins (physiology)
• Protein Binding
• Protein Structure, Tertiary
• Recombinant Fusion Proteins (physiology)
• Sialoglycoproteins (genetics, physiology)
• Sodium-Hydrogen Exchangers (physiology)
• Transfection