Journal article
Inverted Formin 2 Regulates Actin Dynamics by Antagonizing Rho/Diaphanous-related Formin Signaling
Journal of the American Society of Nephrology, Vol.24(6), pp.917-929
06/01/2013
DOI: 10.1681/ASN.2012080834
PMCID: PMC3665394
PMID: 23620398
Abstract
Mutations in inverted formin 2 INF2 are a common cause of familial FSGS. INF2 interacts with diaphanous-related formins (mDia) and antagonizes mDia-mediated actin polymerization in response to active Rho signaling, suggesting that dysregulation of these pathways may mediate the development of INF2-related FSGS. However, the precise mechanisms by which INF2 regulates actin-dependent podocyte behavior remain largely unknown. Here, we investigated the possible role of INF2 in both lamellipodia-associated actin dynamics and actin-dependent slit diaphragm (SD) protein trafficking by manipulating the expression of INF2 and the activity of Rho/mDia signaling in cultured podocytes. Activation of mDia in the absence of INF2 led to defective formation of lamellipodia and abnormal SD trafficking. Effects of mutations disrupting the INF2-mDia interaction suggested the specificity of the mDia-antagonizing effect of INF2 in maintaining the lamellipodium. Furthermore, we found that SD trafficking requires INF2 interaction with lipid raft components. In summary, INF2 regulates lamellipodial actin dynamics and the trafficking of slit diaphragm proteins by opposing Rho/mDia-mediated actin polymerization. Thus, in podocytes, INF2 appears to be an important modulator of actin-dependent behaviors that are under the control of Rho/mDia signaling.
Details
- Title: Subtitle
- Inverted Formin 2 Regulates Actin Dynamics by Antagonizing Rho/Diaphanous-related Formin Signaling
- Creators
- Hua Sun - Shanghai Children's Medical CenterJohannes Schlondorff - Beth Israel Deaconess Medical CenterHenry N. Higgs - Dartmouth CollegeMartin R. Pollak - Beth Israel Deaconess Medical Center
- Resource Type
- Journal article
- Publication Details
- Journal of the American Society of Nephrology, Vol.24(6), pp.917-929
- Publisher
- Amer Soc Nephrology
- DOI
- 10.1681/ASN.2012080834
- PMID
- 23620398
- PMCID
- PMC3665394
- ISSN
- 1046-6673
- eISSN
- 1533-3450
- Number of pages
- 13
- Grant note
- JDY08061 / Research Fund for Young Teachers at Shanghai University K08DK080947 / NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) DK088826; DK080947 / U.S. National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA 81000282/H0502 / Nature Science Foundation of China; National Natural Science Foundation of China (NSFC)
- Language
- English
- Date published
- 06/01/2013
- Academic Unit
- Nephrology, Dialysis and Transplantation; Stead Family Department of Pediatrics
- Record Identifier
- 9984384323302771
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