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Literature summary for 3.6.5.2 extracted from

  • Spuul, P.; Ciufici, P.; Veillat, V.; Leclercq, A.; Daubon, T.; Kramer, I.; Genot, E.
    Importance of RhoGTPases in formation, characteristics, and functions of invadosomes (2014), Small GTPases, 5, e28195.
    View publication on PubMedView publication on EuropePMC

Localization

Localization Comment Organism GeneOntology No. Textmining
invadopodium part of invadosomes, specialized plasma-membrane actin-based microdomains that combine adhesive properties with matrix degrading and/or mechanosensor activities Homo sapiens 71437
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additional information conditions of podosome assembly, detailed overview Homo sapiens
-
-
plasma membrane
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Homo sapiens 5886
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podosome part of invadosomes, specialized plasma-membrane actin-based microdomains that combine adhesive properties with matrix degrading and/or mechanosensor activities Homo sapiens 2102
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Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
GTP + H2O Homo sapiens
-
GDP + phosphate
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens P15153
-
-
Homo sapiens P60953
-
-
Homo sapiens P61586
-
-
Homo sapiens P63000
-
-

Source Tissue

Source Tissue Comment Organism Textmining
dendritic cell
-
Homo sapiens
-
endothelial cell
-
Homo sapiens
-
macrophage
-
Homo sapiens
-
myelomonocytic leukemia cell
-
Homo sapiens
-
osteoclast
-
Homo sapiens
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vascular smooth muscle cell
-
Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
GTP + H2O
-
Homo sapiens GDP + phosphate
-
?

Synonyms

Synonyms Comment Organism
Cdc42
-
Homo sapiens
Rac1
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Homo sapiens
Rac2
-
Homo sapiens
RhoGTPase
-
Homo sapiens

General Information

General Information Comment Organism
malfunction a dominant active mutant of Cdc42 promotes the formation of invadopodia. Small interfering RNA-mediated Fgd1 knockdown inhibits TGFbeta-induced Cdc42 activation and reduces podosome formation and associated extracellular matrix degradation Homo sapiens
malfunction ectopic expression of active RhoA suppresses podosome formation in response to phorbol ester by global inhibition of actin turnover Homo sapiens
malfunction Rac1-deficient macrophages show impaired podosome formation with fewer cells displaying podosomes that lack the adhesion ring, but migrate at a speed similar to that of wild-type macrophages Homo sapiens
malfunction Rac2 deficiency results in complete loss of podosomes in macrophages Homo sapiens
metabolism RhoGTPases are involved in podosome assembly and sequential mechanism for invadopodium formation, regulation, detailed overview Homo sapiens
additional information Rac1 deletion in cathepsin-K+ differentiating Rac2 deficient osteoclasts has no effect on actin ring formation. In contrast to osteoclasts, Rac1 and Rac2 play distinct roles in macrophage podosome formation Homo sapiens
physiological function remodeling of the actin cytoskeleton heavily relies on the regulation of RhoGTPases which have important and conserved roles in almost all its functions. Their activity is tightly regulated by three classes of molecules: guanine nucleotide exchange factors, GEFs, which exchange GDP for GTP hence activating in the hydrolysis of bound GTP to GDP thus contributing to inactivation, and guanine dissociation inhibitors, GDIs, which sequester membrane-anchored GTPases into the cytosol and thus affect their distribution, localization and protein levels. In the mechanism driving invadosome assembly adhesive and soluble ligands act via transmembrane receptors that propagate signals to the cytoskeleton via small G proteins of the Rho family, assisted by tyrosine kinases and scaffold proteins to induce invadosome formation and rearrangements. Oncogene expression and cell-cell interactions may also trigger their assembly Homo sapiens
physiological function remodeling of the actin cytoskeleton heavily relies on the regulation of RhoGTPases which have important and conserved roles in almost all its functions. Their activity is tightly regulated by three classes of molecules: guanine nucleotide exchange factors, GEFs, which exchange GDP for GTP hence activating in the hydrolysis of bound GTP to GDP thus contributing to inactivation, and guanine dissociation inhibitors, GDIs, which sequester membrane-anchored GTPases into the cytosol and thus affect their distribution, localization and protein levels. In the mechanism driving invadosome assembly adhesive and soluble ligands act via transmembrane receptors that propagate signals to the cytoskeleton via small G proteins of the Rho family, assisted by tyrosine kinases and scaffold proteins to induce invadosome formation and rearrangements. Oncogene expression and cell-cell interactions may also trigger their assembly. Osteoclasts generated from the Rac double knockout mouse are devoid of podosomes and sealing zone, and show impaired bone resorption capacities. Rac1 and Rac2 have overlapping roles in podosome assembly and sealing zone-like structure formation by localizing Arp2/3 at podosome sites during osteoclastogenesis.. In contrast to osteoclasts, Rac1 and Rac2 play distinct roles in macrophage podosome formation Homo sapiens
physiological function remodeling of the actin cytoskeleton heavily relies on the regulation of RhoGTPases which have important and conserved roles in almost all its functions. Their activity is tightly regulated by three classes of molecules: guanine nucleotide exchange factors, GEFs, which exchange GDP for GTP hence activating in the hydrolysis of bound GTP to GDP thus contributing to inactivation, e.g. Dock 5, FARP2 (FRG), a Dbl family GEF specific for Rac1. And guanine dissociation inhibitors, GDIs, which sequester membrane-anchored GTPases into the cytosol and thus affect their distribution, localization and protein levels. In the mechanism driving invadosome assembly adhesive and soluble ligands act via transmembrane receptors that propagate signals to the cytoskeleton via small G proteins of the Rho family, assisted by tyrosine kinases and scaffold proteins to induce invadosome formation and rearrangements. Oncogene expression and cell-cell interactions may also trigger their assembly. Osteoclasts generated from the Rac double knockout mouse are devoid of podosomes and sealing zone, and show impaired bone resorption capacities. Rac1 and Rac2 have overlapping roles in podosome assembly and sealing zone-like structure formation by localizing Arp2/3 at podosome sites during osteoclastogenesis. Dock5 and Vav3 regulate Rac1 activation at distinct locations in osteoclasts and at different phases of the bone-resorption cycle Homo sapiens
physiological function remodeling of the actin cytoskeleton heavily relies on the regulation of RhoGTPases which have important and conserved roles in almost all its functions. Their activity is tightly regulated by three classes of molecules: guanine nucleotide exchange factors, GEFs, which exchange GDP for GTP hence activating in the hydrolysis of bound GTP to GDP thus contributing to inactivation, e.g. Fgd1 is the GEF mediating Cdc42 activation and subsequent podosome formation in TGFbeta-stimulated BAE cells. And guanine dissociation inhibitors, GDIs, which sequester membrane-anchored GTPases into the cytosol and thus affect their distribution, localization and protein levels. In the mechanism driving invadosome assembly adhesive and soluble ligands act via transmembrane receptors that propagate signals to the cytoskeleton via small G proteins of the Rho family, assisted by tyrosine kinases and scaffold proteins to induce invadosome formation and rearrangements. Oncogene expression and cell-cell interactions may also trigger their assembly. Essential role of Cdc42 in podosome formation, Cdc42 stands as a central player in the regulation of podosome dynamics as it orchestrates podosome actin polymerization via its canonical effector, WASp. When activated by a GEF, Cdc42 binds to WASp. This binding, together with phosphorylation of WASp on tyrosine, induces a dramatic conformational change. The hydrophobic core is disrupted, releasing the verprolin homology domain-cofilin homology domain-acidic region domain (VCA domain) and enabling its interaction with the Arp2/3 complex, thereby promoting actin nucleation. Constitutively active Cdc42 induces podosome formation in vascular smooth muscle cells Homo sapiens