Cytoskeletal dissociation of ezrin during renal anoxia: role in microvillar injury

Chen, Jing; Doctor, R. Brian; Mandel, Lazaro J.

doi:10.1152/ajpcell.1994.267.3.c784

Cited by 58 publications

(56 citation statements)

References 18 publications

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“…In addition, the ERM proteins are involved in membrane dynamics (11). When ezrin, radixin, and moesin were simultaneously inactivated by antisense treatment in epithelial cells, cell-cell and cell-substratum adhesion was altered (12).…”

mentioning

confidence: 99%

MSAP Is a Novel MIR-interacting Protein That Enhances Neurite Outgrowth and Increases Myosin Regulatory Light Chain

Bornhäuser¹,

Olsson

Lindholm

2003

Journal of Biological Chemistry

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Interactions between the cell membrane and the cytoskeleton play a major role in different aspects of cell differentiation, such as cell motility, cell division, and establishment of cellular architecture. Of particular importance in this context is the association of cortical actin with the cell membrane. The ERM 1 proteins, ezrin, radixin, and moesin, are members of the large 4.1 protein family and are involved in membrane-cytoskeleton interactions. They link the actin cytoskeleton to membranebound proteins located at different membrane sites, i.e. microvilli, membrane ruffles, and cell-cell contacts (1-3). This is accomplished by binding of the C-terminal part of the ERM proteins to actin and of the N-terminal FERM domain to specific membrane proteins (4). FERM domains have been found in many different proteins and are thought to be modules for protein-protein and protein-membrane interactions (5). The ERM proteins are involved in cell adhesion and signal transduction events through phosphorylation (6, 7) and interaction with phosphoinositides (8). The ERM proteins play an important role in the activation of Rho family proteins and can interact both downstream (9) and upstream (10) of Rho.In addition, the ERM proteins are involved in membrane dynamics (11). When ezrin, radixin, and moesin were simultaneously inactivated by antisense treatment in epithelial cells, cell-cell and cell-substratum adhesion was altered (12). Double suppression of radixin and moesin, but not ezrin and radixin or moesin, alters growth cone motility, inhibiting neurite extension (13). In contrast, overexpression of ezrin in insect cells leads to enhanced cell adhesion (14). The mechanisms behind these effects are, however, not well understood, but ERM proteins are known to interact with various proteins such as CD44 and ICAM-1, -2, and -3, which helps in establishing membrane specializations (for review, see Ref. 7). The identification and characterization of further binding partners for ERM proteins can give new insights into the function of these proteins.We have recently identified a novel ERM family protein, MIR, which has an ERM domain at the N terminus and lacks actin binding, instead possessing a RING domain in the Cterminal region (15). Overexpression of MIR abrogated neurite outgrowth in PC12 cells, an effect that may be brought about by its interaction with the myosin regulatory light chain (MRLC). We describe here a novel protein interacting with MIR, called MIR-interacting saposin-like protein (MSAP), which stimulates neurite outgrowth. Sequence comparisons showed that MSAP contains a saposin domain, which is found, among others, in the sphingolipid activator proteins, the saposins (16), and in some saposin-like proteins with a similar structure (17). The effects of MSAP on neurite outgrowth were reduced by MIR. MIR was shown to induce a decrease in the levels of MRLC, which could be blocked by overexpression of MSAP or by inhibition of proteasome activity. Evidence was obtained that the decrease in MRLC levels by MIR invo...

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confidence: 99%

MSAP Is a Novel MIR-interacting Protein That Enhances Neurite Outgrowth and Increases Myosin Regulatory Light Chain

Bornhäuser¹,

Olsson

Lindholm

2003

Journal of Biological Chemistry

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“…A prominent early event during renal ischemia is a distinctive pattern of proximal tubule (PT) brush border disruption consisting of clubbing, blebbing, sloughing, and internalization (3,4). This disruption has been attributed to the dissociation of the plasma membrane from the cytoskeleton within the brush border (5). Nonetheless, little is known regarding the molecular events that disrupt the association of the cell membrane with the brush border cytoskeleton.…”

mentioning

confidence: 99%

“…(iii) Ezrin has been predominantly found in F-actin-containing structures located underneath the plasma membrane in surface protrusions (12)(13)(14)(15), including the intestinal brush border (14), gastric parietal cell microvilli (16), and the renal PT brush border (5,12). (iv) During renal oxygen deprivation, there is a close temporal correlation between microvillar breakdown and the dissociation of ezrin from the microvillar cytoskeleton (5).…”

mentioning

confidence: 99%

“…The purified PT suspensions were preincubated at37°C for 30 min in DMEM/F-12 medium containing 4 mM glycine and gassed with 95% 02/5% CO2 prior to the anoxia protocols. Glycine was utilized due to its protection of the plasma membrane from anoxia-induced damage (22,23), preventing leakage of solubiized ezrin from the anoxic cells (5). After the preincubation period, the PTs were made anoxic for 30 min or 60 min by gassing with 95% N2/5% CO2.…”

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confidence: 99%

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Dephosphorylation of ezrin as an early event in renal microvillar breakdown and anoxic injury.

Chen

Cohn

Mandel

1995

Proc. Natl. Acad. Sci. U.S.A.

103

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Disruption of the renal proximal tubule (PT) brush border is a prominent early event during ischemic injury to the kidney. The molecular basis for this event is unknown. Within the brush border, ezrin may normally link the cytoskeleton to the cell plasma membrane. Anoxia causes ezrin to dissociate from the cytoskeleton and also causes many cell proteins to become dephosphorylated in renal PTs. This study examines the hypothesis that ezrin dephosphorylation accompanies and may mediate the anoxic disruption of the rabbit renal PT. During normoxia, 73 ± 3% of the cytoskeleton-associated (Triton-insoluble) ezrin was phosphorylated, but 88 + 6% of dissociated (Triton-soluble) ezrin was dephosphorylated. Phosphorylation was on serine/threonine residues, since ezrin was not detectable by an antibody against phosphotyrosine. After 60 min of anoxia, phosphorylation of total intracellular ezrin significantly decreased from 72 ± 2% to 21 + 9%6, and ezrin association with the cytoskeleton decreased from 91 + 2% to 58 + 2%. Calyculin A (1 ,uM), the serine/threonine phosphatase inhibitor, inhibited the dephosphorylation of ezrin during anoxia by 57% and also blocked the dissociation of ezrin from the cytoskeleton by 53%. Our results demonstrate that (i) the association of ezrin with the renal microvillar cytoskeleton is correlated with phosphorylation of ezrin serine/threonine residues and (ii) anoxia may cause disruption of the renal brush border by dephosphorylating ezrin and thereby dissociating the brush border membrane from the cytoskeleton.

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“…Several observations suggested that ERM proteins were involved in membrane dynamics [19,20,21] . More recently, several functional analyses demonstrated that they are involved in membrane structures formation.…”

Section: Erm: Functional Insight: 81 Formation Of Cell Surfacementioning

confidence: 99%

Ezrin, Radixin and Moesin: Minor Molecule with Major Impact: A Review

Agarwal¹

2013

IOSR-JDMS

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Cytoskeletal dissociation of ezrin during renal anoxia: role in microvillar injury

Cited by 58 publications

References 18 publications

MSAP Is a Novel MIR-interacting Protein That Enhances Neurite Outgrowth and Increases Myosin Regulatory Light Chain

MSAP Is a Novel MIR-interacting Protein That Enhances Neurite Outgrowth and Increases Myosin Regulatory Light Chain

Dephosphorylation of ezrin as an early event in renal microvillar breakdown and anoxic injury.

Ezrin, Radixin and Moesin: Minor Molecule with Major Impact: A Review

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