podocalyxin; GCTM-2 antigen; Gp200; podocalyxin-like protein 1; PC; PCLP-1 (PODXL, PCLP, PCLP1)

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Function

antiadhesin that maintains an open filtration pathway between neighboring foot processes in the podocyte by charge repulsion
acts as a pro-adhesive molecule, enhancing adherence of cells to immobilized ligands, increasing the rate of migration & cell-cell contacts (integrin-dependent)
induces formation of apical actin-dependent microvilli
role in formation of a preapical plasma membrane subdomain to set up initial epithelial polarization & the apical lumen formation during renal tubulogenesis
monomer; when associated with the membrane raft
oligomer; when integrated in the apical membrane
interacts (via C-terminal PDZ-binding motif DTHL) with SLC9A3R1 (via PDZ domains); the interaction
- is not detected in glomerular epithelial cells
- takes place early in the secretory pathway
- is necessary for its apical membrane sorting
found in a complex with EZR, PODXL & SLC9A3R2
associates with the actin cytoskeleton through complex formation with EZR & SLC9A3R2
interacts (via C-terminal PDZ-binding motif DTHL) with SLC9A3R2 (via PDZ domain 1)
- interaction is detected in glomerular epithelial cells (putative)
interacts with EZR

N- & O-linked glycosylated
sialoglycoprotein
both the O-glycan-rich domain of the extracellular domain & the C-terminus PDZ-binding motif (DTHL) in the cytoplasmic tail harbor an apical sorting signal
cytoplasmic domain is necessary for the apical membrane targeting & renal tubulogenesis
cytoplasmic C-terminus PDZ-binding motif (DTHL) is essential for interaction with SLC9A3R1 & for targeting SLC9A3R1 to the apical cell membrane
extracellular domain is necessary for microvillus formation (putative)
large highly anionic extracellular domain facilitates open filtration pathways between neighboring podocyte foot processes
belongs to the podocalyxin family

apical cell membrane
cell projection, lamellipodium, filopodium, ruffle, microvillus (putative)
membrane raft (putative)
single-pass type 1 membrane protein (putative)
in single attached epithelial cells is restricted to a preapical pole on the free plasma membrane whereas other apical & basolateral proteins are not yet polarized
colocalizes with SLC9A3R2 at the apical plasma membrane during epithelial polarization
colocalizes with SLC9A3R1 at the trans-Golgi network (transiently) & at the apical plasma membrane
its association with the membrane raft is transient
colocalizes with actin filaments, EZR & SLC9A3R1 in a punctate pattern at the apical cell surface where microvilli form
colocalizes with EZR & SLC9A3R2 at the apical cell membrane of glomerular epithelium cells (putative)
forms granular, punctuated pattern, forming patches, preferentially adopting a polar distribution, located on the migrating poles of the cell or forming clusters along the terminal ends of filipodia establishing contact with the endothelial cells
colocalizes with the submembrane actin of lamellipodia, particularly associated with ruffles
colocalizes with vinculin at protrusions of cells
colocalizes with ITGB1

role in regulation of both adhesion & cell morphology & cancer progression
plays a role in cancer development & aggressiveness by inducing cell migration & invasion through its interaction with the actin-binding protein EZR
affects EZR-dependent signaling events, leading to increased activities of the MAPK & PI3K pathways in cancer cells