Polycystin-1 Induces Cell Migration by Regulating Phosphatidylinositol 3-kinase-dependent Cytoskeletal Rearrangements and GSK3β-dependent Cell–Cell Mechanical Adhesion

Boca, Manila; D’Amato, Lisa; Distefano, Gianfranco; Polishchuk, Roman; Germino, Gregory G.; Boletta, Alessandra

doi:10.1091/mbc.e07-02-0142

Cited by 102 publications

(132 citation statements)

References 45 publications

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“…To examine the role of PC1 in regulating G␣ 12 signaling pathways, we utilized previously characterized MDCK cells with overexpression of full-length PC1 (7,28,29). PC1-overexpressing MDCK cells undergo spontaneous tubulogenesis and display resistance to apoptosis through a mechanism that involves activation of the phosphatidylinositol 3-kinase pathway (29).…”

Section: Resultsmentioning

confidence: 99%

Polycystin-1 Protein Level Determines Activity of the Gα12/JNK Apoptosis Pathway

Kong²,

Beaudry

et al. 2010

Journal of Biological Chemistry

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Mutations in PKD1 are the most common cause of autosomal dominant polycystic kidney disease (ADPKD). The protein product of PKD1 (polycystin-1 (PC1)) is a large transmembrane protein with a short intracellular C terminus that interacts with numerous signaling molecules, including G␣ 12 . Cyst formation in ADPKD results from numerous cellular defects, including abnormal cilia, changes in polarity, and dysregulated apoptosis and proliferation. Recently, we reported increased apoptosis in Madin-Darby canine kidney (MDCK) cells through G␣ 12 stimulation of JNK and degradation of the anti-apoptotic protein Bcl-2

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Section: Resultsmentioning

confidence: 99%

Polycystin-1 Protein Level Determines Activity of the Gα12/JNK Apoptosis Pathway

Kong²,

Beaudry

et al. 2010

Journal of Biological Chemistry

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“…45 Defects in cilia signaling, cellular signaling, cell-cell and cell-matrix interactions, which have been observed in ADPKD tubular cysts, probably have a more important role. In addition, as polycystin-1 is known to affect migration and proliferation, 46,47 the absence of Pkd1 might disturb the recruitment of podocytes from the glomerular parietal epithelial cells, which proliferate and migrate into the glomerular tuft and differentiate into podocytes. 48 In conclusion, targeted deletion of Pkd1 in SMCs does not induce major structural blood vessel abnormalities, spontaneously, in mice.…”

Section: Discussionmentioning

confidence: 99%

Pkd1-inactivation in vascular smooth muscle cells and adaptation to hypertension

Hassane¹,

Claij²,

Jodar³

et al. 2011

Laboratory Investigation

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Autosomal dominant polycystic kidney disease (ADPKD) is a multisystem disorder characterized by renal, hepatic and pancreatic cyst formation and cardiovascular complications. The condition is caused by mutations in the PKD1 or PKD2 gene. In mice with reduced expression of Pkd1, dissecting aneurysms with prominent media thickening have been seen. To study the effect of selective disruption of Pkd1 in vascular smooth muscle cells (SMCs), we have generated mice in which a floxed part of the Pkd1 gene was deleted by Cre under the control of the SM22 promotor (SM22-Pkd1 del/del mice). Cre activity was confirmed by X-gal staining using lacZ expressing Cre reporter mice (R26R), and quantitative PCR indicated that in the aorta Pkd1 gene expression was strongly reduced, whereas Pkd2 levels remained unaltered. Histopathological analysis revealed cyst formation in pancreas, liver and kidneys as the result of extravascular Cre activity in pancreatic ducts, bile ducts and in the glomerular Bowman's capsule. Remarkably, we did not find any spontaneous gross structural blood vessel abnormalities in mice with somatic Pkd1 gene disruption in SMCs or simultaneous disruption of Pkd1 in SMCs and endothelial cells (ECs). Extensive isometric myographic analysis of the aorta did not reveal differences in response to KCl, acetylcholine, phenylephrin or serotonin, except for a significant increase in contractility induced by phenylephrin on arteries from 40 weeks old Pkd1 del/ þ germ-line mice. However, SM22-Pkd1 del/del mice showed significantly reduced decrease in heart rate on angiotensin II-induced hypertension. The present findings further demonstrate in vivo, that adaptation to hypertension is altered in SM22-Pkd1 del/del mice.

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“…Expressing TRP channel family member polycystin-1 (PC1) in MDCK cells leads to cytoskeletal rearrangements, increased cell migration, and scattering. 38 In HepG2 cells, HGF stimulation causes calcium influxes through TRPV1 at both plasma membrane and sarcoplasmic reticulum. 39 In MDA-MB-468 cells, EGF induces a calcium influx resulting in an increase in the EMT marker, vimentin.…”

Section: The Case For Intracellular Calciummentioning

confidence: 99%

Control of cell mechanics by RhoA and calcium fluxes during epithelial scattering

2016

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Epithelial tissues use adherens junctions to maintain tight interactions and coordinate cellular activities. Adherens junctions are remodeled during epithelial morphogenesis, including instances of epithelialmesenchymal transition, or EMT, wherein individual cells detach from the tissue and migrate as individual cells. EMT has been recapitulated by growth factor induction of epithelial scattering in cell culture. In culture systems, cells undergo a highly reproducible series of cell morphology changes, most notably cell spreading followed by cellular compaction and cell migration. These morphology changes are accompanied by striking actin rearrangements. The current evidence suggests that global changes in actomyosin-based cellular contractility, first a loss of contractility during spreading and its activation during cell compaction, are the main drivers of epithelial scattering. In this review, we focus on how spreading and contractility might be controlled during epithelial scattering. While we propose a central role for RhoA, which is well known to control cellular contractility in multiple systems and whose role in epithelial scattering is well accepted, we suggest potential roles for additional cellular systems whose role in epithelial cell biology has been less well documented. In particular, we propose critical roles for vesicle recycling, calcium channels, and calcium-dependent kinases.

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Polycystin-1 Induces Cell Migration by Regulating Phosphatidylinositol 3-kinase-dependent Cytoskeletal Rearrangements and GSK3β-dependent Cell–Cell Mechanical Adhesion

Cited by 102 publications

References 45 publications

Polycystin-1 Protein Level Determines Activity of the Gα12/JNK Apoptosis Pathway

Polycystin-1 Protein Level Determines Activity of the Gα12/JNK Apoptosis Pathway

Pkd1-inactivation in vascular smooth muscle cells and adaptation to hypertension

Control of cell mechanics by RhoA and calcium fluxes during epithelial scattering

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