The small GTP-binding protein rac regulates growth factor-induced membrane ruffling

“…Examination of these cells using rhodamine-labeled phalloidin reveals that this engagement of NG2 by the substratum triggers specific types of actin rearrangements, namely, the extension of actincontaining filopodia and lamellipodia. These processes are thought to be mediated by the rho family members cdc42 and rac, respectively [Nobes and Hall, 1995;Ridley et al, 1992], suggesting a role for NG2 in activation of these GTPases. Significantly, we find that the cytoplasmic domain of NG2 is required for these cytoskeletal rearrangements to occur [Fang et al, 1999], demonstrating that this domain of the proteoglycan is likely to be involved in activation of the cytoplasmic signaling cascades associated with cytoskeletal reorganization.…”

mentioning

confidence: 99%

The multi-PDZ domain protein MUPP1 is a cytoplasmic ligand for the membrane-spanning proteoglycan NG2

et al. 2000

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A yeast two-hybrid screen was employed to identify ligands for the cytoplasmic domain of the NG2 chondroitin sulfate proteoglycan. Two overlapping cDNA clones selected in the screen are identical in sequence to a DNA segment coding for the most amino-terminal of the 13 PDZ domains found in the multi-PDZ-protein MUPP1. Antibodies made against recombinant polypeptides representing these two clones (NIP-2 and NIP-7) are reactive with the same 250-kDa molecule recognized by anti-MUPP1 antibodies, confirming the presence of the NIP-2 and NIP-7 sequences in the MUPP1 protein. NIP-2 and NIP-7 GST fusion proteins effectively recognize NG2 in pull-down assays, demonstrating the ability of these polypeptide segments to interact with the intact proteoglycan. The fusion proteins fail to bind NG2 missing the C-terminal half of the cytoplasmic domain, emphasizing the role of the NG2 C-terminus in the interaction with MUPP1. The existence of an NG2/MUPP1 interaction in situ is demonstrated by the ability of NG2 antibodies to co-immunoprecipitate both NG2 and MUPP1 from detergent extracts of cells expressing the two molecules. MUPP1 may serve as a multivalent scaffold that provides a means of linking NG2 with key structural and/or signaling components in the cytoplasm.

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“…Clues as to which of these molecular switches might trigger cable assembly, came initially from tissue culture studies in 3T3 fibroblasts where the small GTPase Rho has been shown to mediate stress fibre assembly in response to extracellular cues, (32) whilst Cdc42 and Rac instead mediate assembly of filopodia and lamellae, respectively. (33,34) Since the wound actin cable is assembled from oriented, bundled stress-fibres, it seemed likely that Rho might be the controlling switch and, indeed, loading of wound edge cells with the Rho blocker, C3 transferase, does prevent actin cable assembly and subsequent re-epithelialisation of the wound, whilst blocking Rac from firing does not inhibit reepithelialisation. (31) The primary cues at the time of wounding that might activate Rho remain largely elusive.…”

Section: Introductionmentioning

confidence: 99%

Conserved mechanisms of repair: from damaged single cells to wounds in multicellular tissues

Woolley

Martin

2000

Bioessays

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The capacities to repair minor membrane holes in damaged single cells, and the more major damage sustained when a multicellular tissue is wounded, both involve a series of ancient and highly conserved processes. In this review, we discuss what is known about how the plasma membrane of a single cell and its underlying cortical cytoplasm are repaired following cell damage, and how multicellular wounds to the embryonic and adult skin are also able to heal. Pivotal for all these processes is the actin cytoskeleton and we draw analogies between the actin machineries that drive repair and those that appear to underlie several genetically tractable morphogenetic processes that occur during Drosophila and Caenorhabditis elegans embryogenesis.

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The small GTP-binding protein rac regulates growth factor-induced membrane ruffling

Cited by 253 publications

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Redistribution of Bruton's tyrosine kinase by activation of phosphatidylinositol 3-kinase and Rho-family GTPases

Redistribution of Bruton's tyrosine kinase by activation of phosphatidylinositol 3-kinase and Rho-family GTPases

The multi-PDZ domain protein MUPP1 is a cytoplasmic ligand for the membrane-spanning proteoglycan NG2

Conserved mechanisms of repair: from damaged single cells to wounds in multicellular tissues

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