Cofilin Interacts with ClC-5 and Regulates Albumin Uptake in Proximal Tubule Cell Lines

Hryciw, Deanne H.; Wang, Yinghong; Devuyst, Olivier; Pollock, Carol; Poronnik, Philip; Guggino, William B.

doi:10.1074/jbc.m307890200

Cited by 87 publications

(109 citation statements)

References 46 publications

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“…Peak recruitment of the actin-severing protein cofilin [55] and the Arp2/3 suppressor coronin [56] were both significantly skewed post-scission, suggesting an ordered shut down of the actin polymerization machinery and disassembly of scission-associated actin ( Figure 4D). …”

Section: Sequential Recruitment Of Positive and Negative Regulators Omentioning

confidence: 97%

A High Precision Survey of the Molecular Dynamics of Mammalian Clathrin-Mediated Endocytosis

Perrais²,

2011

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Dual colour total internal reflection fluorescence microscopy is a powerful tool for decoding the molecular dynamics of clathrin-mediated endocytosis (CME). Typically, the recruitment of a fluorescent protein-tagged endocytic protein was referenced to the disappearance of spot-like clathrin-coated structure (CCS), but the precision of spot-like CCS disappearance as a marker for canonical CME remained unknown. Here we have used an imaging assay based on total internal reflection fluorescence microscopy to detect scission events with a resolution of ,2 s. We found that scission events engulfed comparable amounts of transferrin receptor cargo at CCSs of different sizes and CCS did not always disappear following scission. We measured the recruitment dynamics of 34 types of endocytic protein to scission events: Abp1, ACK1, amphiphysin1, APPL1, Arp3, BIN1, CALM, CIP4, clathrin light chain (Clc), cofilin, coronin1B, cortactin, dynamin1/ 2, endophilin2, Eps15, Eps8, epsin2, FBP17, FCHo1/2, GAK, Hip1R, lifeAct, mu2 subunit of the AP2 complex, myosin1E, myosin6, NECAP, N-WASP, OCRL1, Rab5, SNX9, synaptojanin2b1, and syndapin2. For each protein we aligned ,1,000 recruitment profiles to their respective scission events and constructed characteristic ''recruitment signatures'' that were grouped, as for yeast, to reveal the modular organization of mammalian CME. A detailed analysis revealed the unanticipated recruitment dynamics of SNX9, FBP17, and CIP4 and showed that the same set of proteins was recruited, in the same order, to scission events at CCSs of different sizes and lifetimes. Collectively these data reveal the fine-grained temporal structure of CME and suggest a simplified canonical model of mammalian CME in which the same core mechanism of CME, involving actin, operates at CCSs of diverse sizes and lifetimes.

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Section: Sequential Recruitment Of Positive and Negative Regulators Omentioning

confidence: 97%

A High Precision Survey of the Molecular Dynamics of Mammalian Clathrin-Mediated Endocytosis

Perrais²,

2011

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“…Our case seems to suggest instead that the cooperation between the two proteins might go beyond renal tubular function. We speculate that, as both the OCRL1 and the ClC-5 proteins are linked through their C-terminal domains to actin dynamics, [27][28][29] perturbation of the fine mechanisms of cell polarity 30,31 and/or cytokinesis 32 might be additional common pathogenic mechanisms.…”

Section: Resultsmentioning

confidence: 98%

An atypical Dent’s disease phenotype caused by co-inheritance of mutations at CLCN5 and OCRL genes

et al. 2012

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Dent's disease is an X-linked renal tubulopathy caused by mutations mainly affecting the CLCN5 gene. Defects in the OCRL gene, which is usually mutated in patients with Lowe syndrome, have been shown to lead to a Dent-like phenotype called Dent disease 2. However, about 20% of patients with Dent's disease carry no CLCN5/OCRL mutations. The disease's genetic heterogeneity is accompanied by interfamilial and intrafamilial phenotypic heterogeneity. We report on a case of Dent's disease with a very unusual phenotype (dysmorphic features, ocular abnormalities, growth delay, rickets, mild mental retardation) in which a digenic inheritance was discovered. Two different, novel disease-causing mutations were detected, both inherited from the patient's healthy mother, that is a truncating mutation in the CLCN5 gene (A249fs*20) and a donor splice-site alteration in the OCRL gene (c.388 þ 3A4G). The mRNA analysis of the patient's leukocytes revealed an aberrantly spliced OCRL mRNA caused by in-frame exon 6 skipping, leading to a shorter protein, but keeping intact the central inositol 5-phosphatase domain and the C-terminal side of the ASH-RhoGAP domain. Only wild-type mRNA was observed in the mother's leukocytes due to a completely skewed X inactivation. Our results are the first to reveal the effect of an epistatic second modifier in Dent's disease too, which can modulate its expressivity. We surmise that the severe Dent disease 2 phenotype of our patient might be due to an addictive interaction of the mutations at two different genes.

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“…The presence of albumin causes actin clusters to form at the apical membrane that colocalize with the sites of albumin uptake (21). We have also shown that an interaction between ClC-5 and the actin-depolymerizing protein cofilin is required for albumin uptake (22). Thus, although significant progress has been made in identifying both ClC-5 and NHE3, as essen-tial and therefore rate-limiting components in albumin uptake, we have little insight into the protein-protein interactions that direct the formation of the endocytic complex and anchor it to the cytoskeleton.…”

mentioning

confidence: 84%

“…Materials and Antibodies-Anti-NHERF1 (35), anti-NHERF2 (20) and anti-ClC-5 antibody have been previously described (22,36). Anti-GST conjugated to horseradish peroxidase (HRP) was provided by Amersham Biosciences, and anti-MBP conjugated to HRP was provided by New England Biolabs.…”

Section: Methodsmentioning

confidence: 99%

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Regulation of Albumin Endocytosis by PSD95/Dlg/ZO-1 (PDZ) Scaffolds

Hryciw

Ekberg

Ferguson

et al. 2006

Journal of Biological Chemistry

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The constitutive reuptake of albumin from the glomerular filtrate by receptor-mediated endocytosis is a key function of the renal proximal tubules. Both the Cl ؊ channel ClC-5 and the Na ؉ -H ؉ exchanger isoform 3 are critical components of the macromolecular endocytic complex that is required for albumin uptake, and therefore the cell-surface levels of these proteins may limit albumin endocytosis. This study was undertaken to investigate the potential roles of the epithelial PDZ scaffolds, Na ؉ -H ؉ exchange regulatory factors, NHERF1 and NHERF2, in albumin uptake by opossum kidney (OK) cells. We found that ClC-5 co-immunoprecipitates with NHERF2 but not NHERF1 from OK cell lysate. Experiments using fusion proteins demonstrated that this was a direct interaction between an internal binding site in the C terminus of ClC-5 and the PDZ2 module of NHERF2. In OK cells, NHERF2 is restricted to the intravillar region while NHERF1 is located in the microvilli. Silencing NHERF2 reduced both cell-surface levels of ClC-5 and albumin uptake. Conversely, silencing NHERF1 increased cell-surface levels of ClC-5 and albumin uptake, presumably by increasing the mobility of NHE3 in the membrane and its availability to the albumin uptake complex. Surface biotinylation experiments revealed that both NHERF1 and NHERF2 were associated with the plasma membrane and that NHERF2 was recruited to the membrane in the presence of albumin. The importance of the interaction between NHERF2 and the cytoskeleton was demonstrated by a significant reduction in albumin uptake in cells overexpressing an ezrin binding-deficient mutant of NHERF2. Thus NHERF1 and NHERF2 differentially regulate albumin uptake by mechanisms that ultimately alter the cell-surface levels of ClC-5.

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Cofilin Interacts with ClC-5 and Regulates Albumin Uptake in Proximal Tubule Cell Lines

Cited by 87 publications

References 46 publications

A High Precision Survey of the Molecular Dynamics of Mammalian Clathrin-Mediated Endocytosis

A High Precision Survey of the Molecular Dynamics of Mammalian Clathrin-Mediated Endocytosis

An atypical Dent’s disease phenotype caused by co-inheritance of mutations at CLCN5 and OCRL genes

Regulation of Albumin Endocytosis by PSD95/Dlg/ZO-1 (PDZ) Scaffolds

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