title: Expression of podocalyxin enhances the adherence, migration, and intercellular communication of cells.
abstract: Podocalyxin (PODXL) is an anti-adhesive glycoprotein expressed abundantly in the epithelial cells of kidney glomeruli. In contrast, we report herein that expression of podocalyxin(GFP) (PODXL(GFP)) in CHO cells increased the adherence to immobilized fibronectin, spreading, and migration. The transient knockdown of PODXL or the expression of PODXL lacking the cytosolic carboxyterminal domain (PODXL-Delta(451)) inhibited cell adherence. Moreover, the effect of PODXL was prevented by the ectodomain of podocalyxin (PODXL-Delta(429)), by RGD peptides, or by inhibitors of the vitronectin receptor (alphavbeta3). CHO-PODXL(GFP) also showed adherence to human vascular endothelial cells (HUVEC), exhibiting polarization of granular PODXL and emission of long and thin, spike-like, protrusions with PODXL granules progressing along. We found PODXL colocalized with beta1 integrins at membrane ruffle regions on the leading edge of the cell and a blocking beta1 mAb prevented the spreading of cells. PODXL was also associated with submembrane actin in lamellipodia ruffles, or with vinculin at cell protrusions. The proadhesive effects of PODXL were absent in sialic acid deficient O-glycomutant CHO cells. To conclude, we present evidence indicating that human PODXL enhances the adherence of cells to immobilized ligands and to vascular endothelial cells through a mechanism(s) dependent on the activity of integrins.
authors.affiliation: Department of Physiopathology, Centro de Investigaciones Biológicas (CSIC), Spain.
authors.forename: Susana
authors.initials: S
authors.lastname: Larrucea
authors.forename: Nora
authors.initials: N
authors.lastname: Butta
authors.forename: Elena G
authors.initials: EG
authors.lastname: Arias-Salgado
authors.forename: Sonia
authors.initials: S
authors.lastname: Alonso-Martin
authors.forename: Matilde S
authors.initials: MS
authors.lastname: Ayuso
authors.forename: Roberto
authors.initials: R
authors.lastname: Parrilla
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D016466:CHO Cells; D002448:Cell Adhesion / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D006224:Cricetinae; D003412:Cricetulus; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D039564:Integrin alphaV / Q000378:metabolism; D039302:Integrin alphaVbeta3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D019012:Integrin beta1 / Q000378:metabolism; D051379:Mice; D009842:Oligopeptides / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012795:Sialoglycoproteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D016596:Vinculin / Q000378:metabolism
chemical_list: D000199:Actins; D039564:Integrin alphaV; D039302:Integrin alphaVbeta3; D019012:Integrin beta1; D009842:Oligopeptides; D011993:Recombinant Fusion Proteins; D012795:Sialoglycoproteins; C001643:podocalyxin; D016596:Vinculin; C046617:arginyl-glycyl-aspartyl-serine