Altered distribution and co-localization of polycystin-2 with polycystin-1 in MDCK cells after wounding stress

Scheffers, M. S.; Bent, Paola van der; Wal, Annemieke van de; Eendenburg, Jaap van; Breuning, Martijn H.; Heer, Emile de; Peters, Dorien J.M.

doi:10.1016/j.yexcr.2003.08.019

Cited by 19 publications

(13 citation statements)

References 53 publications

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“…The spread cells can thus revert to their original cuboidal morphology, at which point their growth and division are contact-inhibited again. This hypothesis is consistent with another recent study in MDCK cells (Scheffers et al, 2004).…”

Section: Wound Closure In Cultured Epithelial Cells Provides a Tractablesupporting

confidence: 94%

Multiple rows of cells behind an epithelial wound edge extend cryptic lamellipodia to collectively drive cell-sheet movement

Farooqui

Fenteany

2005

Journal of Cell Science

384

373

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The mechanism by which epithelial, endothelial and other strongly cell-cell adhesive cells migrate collectively as continuous sheets is not clear, even though this process is crucial for embryonic development and tissue repair in virtually all multicellular animals. Wound closure in Madin-Darby canine kidney (MDCK) epithelial cell monolayers involves Rac GTPase-dependent migration of cells both at and behind the wound edge. We report here for the first time that cells behind the margin of wounded MDCK cell monolayers, even hundreds of microns from the edge, extend `cryptic' lamellipodia against the substratum beneath cells in front of them, toward the wound, as determined by confocal, two-photon and transmission electron microscopy. These so-called submarginal cells nevertheless strictly maintain their more apical cell-cell contacts when they migrate as part of a coherent cell sheet, hiding their basal protrusions from conventional microscopy. The submarginal protrusions display the hallmarks of traditional lamellipodia based on morphology and dynamics. Cells behind the margin therefore actively crawl, instead of just moving passively when cells at the margin pull on them. The rate of migration is inversely proportional to the distance from the margin, and cells move co-ordinately, yet still in part autonomously, toward the wound area. We also clarify the ancillary role played by nonprotrusive contractile actin bundles that assemble in a Rho GTPase-dependent manner at the margin after wounding. In addition, some cell proliferation occurs at a delay after wounding but does not contribute to closure. Instead, it apparently serves to replace damaged cells so that intact spread cells can revert to their normal cuboidal morphology and the original cell density of the unbroken sheet can be restored.

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Section: Wound Closure In Cultured Epithelial Cells Provides a Tractablesupporting

confidence: 94%

Multiple rows of cells behind an epithelial wound edge extend cryptic lamellipodia to collectively drive cell-sheet movement

Farooqui

Fenteany

2005

Journal of Cell Science

384

373

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“…In terms of their subcellular localizations, TRP channels have been localized in various subcellular sites such as plasma membrane [12], endoplasmic reticulum [16], lysosomes [17][18][19], and primary cilium [20][21][22]. Consistently, PKD2 expression has been reported in the plasma membrane [23,24], ER [25], primary cilium [26], centrosome [27], and mitotic spindles in dividing cells [28]. Specific functions of PKD2 have been associated with its expression in the plasma membrane, ER, and primary cilium (Fig.…”

Section: Introductionmentioning

confidence: 87%

Cell biology of polycystin-2

Tsiokas¹,

Kim²,

Ong³

2007

Cellular Signalling

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Naturally occurring mutations in two separate, but interacting loci, pkd1 and pkd2 are responsible for almost all cases of autosomal dominant polycystic kidney disease (ADPKD). ADPKD is one of the most common genetic diseases resulting primarily in the formation of large kidney, liver, and pancreatic cysts. Homozygous deletion of either pkd1 or pkd2 results in embryonic lethality in mice due to kidney and heart defects illustrating their indispensable roles in mammalian development. However, the mechanism by which mutations in these genes cause ADPKD and other developmental defects are unknown. Research in the past several years has revealed that PKD2 has multiple functions depending on its subcellular localization. It forms a receptor-operated, non-selective cation channel in the plasma membrane, a novel intracellular Ca 2+ release channel in the endoplasmic reticulum (ER), and a mechanosensitive channel in the primary cilium. This review focuses on the functional compartmentalization of PKD2, its modes of activation, and PKD2-mediated signal transduction.

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“…Heterologously expressed, epitope-tagged PC2 traffics into cilia once they form in post-confluent monolayers but the fulllength epitope-tagged protein still cannot be detected on the remainder of the plasma membrane . Although a cell surface location of endogenous PC2 has been reported using a variety of native protein antisera Scheffers et al, 2004;Li et al, 2005), none of these studies showed expression of epitope tagged PC2 in the plasma membrane. This has led to some controversy regarding PC2 expression in the plasma membrane outside cilia (reviewed by Witzgall, 2005).…”

Section: Primary Cilia Play a Key Role In The Pathogenesis Of Autosommentioning

confidence: 99%

Polycystin-2 traffics to cilia independently of polycystin-1 by using an N-terminal RVxP motif

Geng

Okuhara

et al. 2006

Journal of Cell Science

267

220

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Primary cilia play a key role in the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD). The affected proteins, polycystin-1 (PC1) and polycystin-2 (PC2), interact with each other and are expressed in cilia. We found that COOH-terminal truncated PC2 (PC2-L703X), lacking the PC1 interaction region, still traffics to cilia. We examined PC2 expression in several tissues and cells lacking PC1 and found that PC2 is expressed in cilia independently of PC1. We used N-terminal deletion constructs to narrow the domain necessary for cilia trafficking to the first 15 amino acids of PC2 and identified a conserved motif, R6VxP, that is required for cilial localization. The N-terminal 15 amino acids are also sufficient to localize heterologous proteins in cilia. PC2 has endogenous cilia trafficking information and is present in cilia of cells lining cysts that result from mutations in PKD1.

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Altered distribution and co-localization of polycystin-2 with polycystin-1 in MDCK cells after wounding stress

Cited by 19 publications

References 53 publications

Multiple rows of cells behind an epithelial wound edge extend cryptic lamellipodia to collectively drive cell-sheet movement

Multiple rows of cells behind an epithelial wound edge extend cryptic lamellipodia to collectively drive cell-sheet movement

Cell biology of polycystin-2

Polycystin-2 traffics to cilia independently of polycystin-1 by using an N-terminal RVxP motif

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