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Query: UMLS:C0344329 (collapse)
 28,634 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ERM protein--ezrin, radixin, moesin--localize to a variety of cortical structures, where they may participate in connecting the cytoskeleton to components of the plasma membrane. Antibodies that recognize the ERM proteins specifically stain growth cones of various neurons [Goslin et al., 1989: J. Cell Biol. 109:1621-1631; Birgbauer et al., 1991: J. Neurosci. Res. 30:232-241]. To probe the function of ERM proteins in growth cones, we studied the consequences of perturbing growth cone morphology and motility of cultured chick sympathetic neurons. We demonstrate that radixin is present in these growth cones. Withdrawal of nerve growth factor (NGF) induces rapid collapse of the growth cones; concomitantly, radixin staining in these growth cones are greatly diminished. Upon readdition of NGF, rapid growth cone formation is accompanied by relocalization of radixin. Induction of growth cone collapse by either growth cone-growth cone contact or exposure to brain membrane extract results in a similar diminution of radixin staining. We induced a more subtle change in the organization of the growth cones by subjecting them to an electric field. These growth cones rapidly orient toward the cathode. We show that the radixin staining of the growth cones is also asymmetrically localized toward the leading edges in the new direction of growth. The results suggest that the localization of radixin may be essential for the normal expression of growth cone morphology and function.
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PMID:Response of radixin to perturbations of growth cone morphology and motility in chick sympathetic neurons in vitro. 876 24

Normal and transformed human cells when stained for ezrin, an F-actin-binding ERM (ezrin/radixin/moesin) family protein, revealed a faint and intense immunofluorescence, respectively. Surprisingly, nuclear staining that was assigned to the nucleolus by confocal laser and immunoelectron microscopy was detected in both cell types and was more prominent in normal cells due to the absence of glistering cytoplasmic fluorescence. By Western analysis the nuclear fraction was seen to have a 55-kDa ezrin-reactive protein that did not react to the antibodies raised against the C-terminus of the protein, suggesting that it may correspond to an endogenously cleaved N-terminus of the protein. Transfections of cells with a cDNA encoding full-length ezrin tagged with green fluorescent protein (GFP) at its N-terminus indeed resulted in two GFP-tagged products corresponding to full-length and 55-kDa endogenously cleaved forms. Transfection with a cDNA encoding approximately 55 kDa of the ezrin N-terminus (N-ezrin) showed that it can translocate to the nucleus. N-ezrin transfected cells exhibited irregular cell edges and collapse of actin fibers. Similar changes were seen following microinjection of anti-p81/ezrin antibody, suggesting that N-ezrin may function as a dominant negative competitor of ezrin. These data demonstrate the existence of an N-terminal cleavage form of ezrin that localizes to the nucleolus and that its overexpression induces cytoskeletal changes.
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PMID:Identification of a 55-kDa ezrin-related protein that induces cytoskeletal changes and localizes to the nucleolus. 1038 20

Chemokine-induced polarization of lymphocytes involves the rapid collapse of vimentin intermediate filaments (IFs) into an aggregate within the uropod. Little is known about the interactions of lymphocyte vimentin with other cytoskeletal elements. We demonstrate that human peripheral blood T lymphocytes express plectin, an IF-binding, cytoskeletal cross-linking protein. Plectin associates with a complex of structural proteins including vimentin, actin, fodrin, moesin, and lamin B in resting peripheral blood T lymphocytes. During chemokine-induced polarization, plectin redistributes to the uropod associated with vimentin and fodrin; their spatial distribution indicates that this vimentin-plectin-fodrin complex provides a continuous linkage from the nucleus (lamin B) to the cortical cytoskeleton. Overexpression of the plectin IF-binding domain in the T cell line Jurkat induces the perinuclear aggregation of vimentin IFs. Plectin is therefore likely to serve as an important organizer of the lymphocyte cytoskeleton and may regulate changes of lymphocyte cytoarchitecture during polarization and extravasation.
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PMID:Cutting edge: integration of human T lymphocyte cytoskeleton by the cytolinker plectin. 1144 Oct 66

CD3/CD28-induced activation of the PI3/Akt kinase pathway and proliferation is impaired in T cells after contact with the measles virus (MV) glycoprotein (gp) complex. We now show that this signal also impairs actin cytoskeletal remodeling in T cells, which loose their ability to adhere and to promote microvilli formation. MV exposure results in an almost complete collapse of membrane protrusions associated with reduced phosphorylation levels of cofilin and ezrin/radixin/moesin (ERM) proteins. Consistent with their inability to activate Cdc42 and Rac1 in response to the ligation of CD3/CD28, T cells exposed to MV fail to acquire a morphology consistent with spreading and lamellopodia formation. In spite of these impairments of cytoskeleton-driven morphological alterations, these cells are recruited into conjugates with dendritic cells as efficiently as control T cells. The signal elicited by MV, however, prevents T cells to polarize as documented by a failure to redistribute the microtubule organizing center toward the synapse. Moreover, CD3 cannot be efficiently clustered and redistributed to the central region of the immunological synapse. Thus, by inducing microvillar collapse and interfering with cytoskeletal remodeling, MV signaling disturbs the ability of T cells to adhere, spread, and cluster receptors essential for sustained T-cell activation.
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PMID:Measles virus contact with T cells impedes cytoskeletal remodeling associated with spreading, polarization, and CD3 clustering. 1678 97

Close homolog of L1 (CHL1) is a transmembrane cell adhesion molecule with unique developmental functions in cortical neuronal positioning and dendritic projection within the L1 family, as well as shared functions in promotion of integrin-dependent neurite outgrowth and semaphorin3A (Sema3A)-mediated axon repulsion. The molecular mechanisms by which CHL1 mediates these diverse functions are obscure. Here it is demonstrated using a cytofluorescence assay that CHL1 is able to recruit ezrin, a member of the ezrin-radixin-moesin (ERM) family of filamentous actin binding proteins to the plasma membrane, and that this requires a membrane-proximal motif (RGGKYSV) in the CHL1 cytoplasmic domain. This sequence in CHL1 is shown to have novel functions necessary for Sema3A-induced growth cone collapse and CHL1-dependent neurite outgrowth and branching in cortical embryonic neurons. In addition, stimulation of haptotactic cell migration and cellular adhesion to fibronectin by CHL1 depends on the CHL1/ERM recruitment motif. These findings suggest that a direct or indirect interaction between CHL1 and ERM proteins mediates Sema3A-induced growth cone collapse as well as neurite outgrowth and branching, which are essential determinants of axon guidance and connectivity in cortical development.
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PMID:CHL1 promotes Sema3A-induced growth cone collapse and neurite elaboration through a motif required for recruitment of ERM proteins to the plasma membrane. 1799 39

Ezrin-radixin-moesin (ERM) proteins are involved in the linkage of membranes to theactin filament (F-actin) cytoskeleton. Phosphorylation of the C-terminus activates the F-actin binding domain of ERM proteins by preventing the action of an autoinhibitory domain. In this study, we investigated whether a growth cone collapsing signal, semaphorin 3A (Sema3A), alters the state of ERM C-terminus phosphorylation. In the growth cones of dorsal root ganglion axons, phosphorylated ERM proteins localize to filopodia. We report that Sema3A inhibits ERM protein phosphorylation in growth cone filopodia. Significantly, Sema3A decreased ERM phosphorylation prior to the onset of growth cone collapse. Over-expression of the F-actin binding fragment of ERM proteins, which competes with endogenous ERM proteins for binding to F-actin, inhibited filopodial initiation and dynamics. Sema3A has been previously shown to inhibit phosphoinositide 3-kinase (PI3K) activity. Inhibition of PI3K resulted in the loss of phosphorylated ERM proteins from growth cone filopodia, and treatment with a PI3K activating peptide blocked the effects of Sema3A on ERM phosphorylation. Collectively, these observations demonstrate that inactivation of PI3K in response to Sema3A results in decreased phosphorylation of ERM proteins in filopodia thereby contributing to growth cone collapse.
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PMID:Semaphorin 3A inhibits ERM protein phosphorylation in growth cone filopodia through inactivation of PI3K. 1832 64

Axonal growth cones initiate and sustain directed growth in response to cues in their environment. A variety of events such as receptor internalization, kinase activation, and actin rearrangement can be stimulated by guidance cues and are essential for mediating targeted growth cone behavior. Surprisingly little is known about how such disparate actions are coordinated. Our data suggest that ezrin, radixin, and moesin (ERMs), a family of highly homologous, multifunctional proteins may be able to coordinate growth cone responses to the guidance cue Semaphorin 3A (Sema3A). We show that active ERMs concentrate asymmetrically in neocortical growth cones, are rapidly and transiently inactivated by Sema3A, and are required for Sema3A-mediated growth cone collapse and guidance. The FERM domain of active ERMs regulates internalization of the Sema3A receptor, Npn1, and its coreceptor, L1CAM, while the ERM C-terminal domain binds and caps F-actin. Our data support a model in which ERMs can coordinate membrane and actin dynamics in response to Sema3A.
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PMID:ERM proteins regulate growth cone responses to Sema3A. 1865 36

Axonal growth cones turn away from repulsive guidance cues. This may start with reduced protrusive motility in the region the growth cone leading margin that is closer to the source of repulsive cue. Using explants of E7 chick temporal retina, we examine the effects of two repulsive guidance cues, ephrin-A2 and slit3, on retinal ganglion cell growth cone protrusive activity, total F-actin, free F-actin barbed ends, and the activities (phosphorylation states) of actin regulatory proteins, ADF/cofilin and ezrin, radixin, moesin (ERM) proteins. Ephrin-A2 rapidly stops protrusive activity simultaneously with reducing F-actin, free barbed ends and the activities of ADF/cofilin and ERM proteins. Slit3 also stops protrusion and reduces the activities of ADF/cofilin and ERM proteins. We interpret these results as indicating that repulsive guidance cues inhibit actin polymerization and actin-membrane linkage to stop protrusive activity. Retrograde F-actin flow withdraws actin to the C-domain, where F-actin bundles interact with myosin II to generate contractile forces that can collapse and retract the growth cone. Our results suggest that common mechanisms are used by repulsive guidance cue to disable growth cone motility and remodel growing axon terminals.
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PMID:Repulsive axon guidance cues ephrin-A2 and slit3 stop protrusion of the growth cone leading margin concurrently with inhibition of ADF/cofilin and ERM proteins. 2232 20

Pseudomonas aeruginosa is a major human opportunistic pathogen and one of the most important causal agents of bacteremia. For non-blood-borne infection, bacterial dissemination requires the crossing of the vascular endothelium, the main barrier between blood and the surrounding tissues. Here, we investigated the effects of P. aeruginosa type 3 secretion effectors, namely ExoS, ExoT, and ExoY, on regulators of actin cytoskeleton dynamics in primary endothelial cells. ExoS and ExoT similarly affected the Lim kinase-cofilin pathway, thereby promoting actin filament severing. Cofilin activation was also observed in a mouse model of P. aeruginosa-induced acute pneumonia. Rho, Rac, and Cdc42 GTPases were sequentially inactivated, leading to inhibition of membrane ruffling, filopodia, and stress fiber collapse, and focal adhesion disruption. At the end of the process, ExoS and ExoT produced a dramatic retraction in all primary endothelial cell types tested and thus a rupture of the endothelial monolayer. ExoY alone had no effect in this context. Cell retraction could be counteracted by overexpression of actin cytoskeleton regulators. In addition, our data suggest that moesin is neither a direct exotoxin target nor an important player in this process. We conclude that any action leading to inhibition of actin filament breakdown will improve the barrier function of the endothelium during P. aeruginosa infection.
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PMID:Sequential inactivation of Rho GTPases and Lim kinase by Pseudomonas aeruginosa toxins ExoS and ExoT leads to endothelial monolayer breakdown. 2397 44

Early postnatal mouse cochlear cultures were treated with a small panel of kinase inhibitors to elucidate the mechanisms underlying the maintenance of hair-bundle structure in the developing inner ear. At low concentrations (1-10 nM), staurosporine causes the collapse and loss of hair bundles without provoking hair-cell death, as judged by lack of terminal transferase dUTP nick end labeling (TUNEL) labeling or reactivity to anti-activated caspase-3. Staurosporine exposure results in the fusion of the hair bundle's stereocilia, a resorption of the parallel actin bundles of the stereocilia into the cytoplasm of the hair cell, a detachment of the apical, non-stereociliary membrane of the hair cell from the underlying cuticular plate, and a severing of the hair-bundle's rootlets from the actin cores of the stereocilia. It does not block membrane retrieval at the apical pole of the hair cells, nor does it elicit the externalization of phosphatidylserine. Staurosporine treatment causes a reduction in levels of the phosphorylated forms of ezrin, radixin, and moesin in cochlear cultures during the period of hair-bundle loss, indicating the integrity of the hair bundle may be actively maintained by the phosphorylation status of these proteins.
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PMID:Staurosporine-induced collapse of cochlear hair bundles. 2470 Jan 9


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