Role of isoprenoids in cytoskeleton integrity and albumin endocytosis by opossum kidney cells

McTaggart, Steven J., Eitle, Eveline, Harris, Peter J. and Jones, Colin L. (2004) Role of isoprenoids in cytoskeleton integrity and albumin endocytosis by opossum kidney cells. Nephron Experimental Nephrology, 97 3: e77-e85. doi:10.1159/000078641


Author McTaggart, Steven J.
Eitle, Eveline
Harris, Peter J.
Jones, Colin L.
Title Role of isoprenoids in cytoskeleton integrity and albumin endocytosis by opossum kidney cells
Journal name Nephron Experimental Nephrology   Check publisher's open access policy
ISSN 1660-2129
Publication date 2004-07-01
Sub-type Article (original research)
DOI 10.1159/000078641
Open Access Status Not yet assessed
Volume 97
Issue 3
Start page e77
End page e85
Total pages 9
Place of publication Basel, Switzerland
Publisher S. Karger AG
Language eng
Formatted abstract
Background: The actin cytoskeleton has been increasingly implicated in endocytic events that are involved in the reabsorption of filtered protein by the proximal tubule. Isoprenylated small G proteins have emerged as key regulators of the actin cytoskeleton. This study examines the role of isoprenoid intermediates in organization of the cytoskeleton, and the effect of modification of the cytoskeleton on albumin endocytosis.

Methods: The effect of lovastatin on cytoskeleton morphology of opossum kidney cells (OK cells) was determined by staining with fluorescent isothiocyanate (FITC)-phalloidin followed by examination using confocal microscopy. Quantitative effects on albumin binding and uptake were determined using a well-established method.

Results: Inhibition of isoprenoid synthesis by lovastatin led to morphological disruption of the cytoskeleton with a concentration-dependent decrease in albumin uptake into OK cells. Addition of mevalonate, but not cholesterol, ameliorated the effects of lovastatin on the cytoskeleton and albumin uptake. Selective inhibition of isoprenoid intermediates with a farnesyltransferase inhibitor suggests that geranylgeranylated proteins mediate cytoskeleton organization.

Conclusion: These results confirm the importance of cytoskeleton integrity in albumin endocytosis in renal proximal tubules. While the present data suggest that synthesis of isoprenoids via the mevalonate pathway is a critical step in maintenance of the cytoskeleton, the role of individual small G proteins in control of the cytoskeleton and other endocytic events is yet to be defined. Copyright
Keyword Cytoskeleton
Endocytosis
Isoprenoids
Proteinuria
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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