Disease relevance of Rhod

• These findings identify a cell-autonomous defect of convergent extension, requiring PCP signalling via RhoA-Rho kinase, during the development of severe neural tube defects in the mouse [1].
• We also showed that the recovery from demyelination in cuprizone-treated and aged mice is achieved after administration of the herbal medicine Ninjin'yoeito, an effective therapy targeting the FcRgamma/Fyn-Rho (Rac1)-MAPK (P38 MAPK)-p-MBPs signaling cascade [2].

High impact information on Rhod

• Endosome dynamics regulated by a Rho protein [3].
• Activated RhoD causes rearrangements of the actin cytoskeleton and cell surface, and governs early endosome motility and distribution [3].
• In all, this suggests that a small GTPase Rho and Rho kinase have a pivotal role in MCP-1-induced junction disarrangement [4].
• Enhancement of the stress fibers by RhoA or RhoA-activating lysophosphatidic acid was reversed by the transfection of RhoD cDNA [5].
• These results imply that RhoD does not affect nuclear division but can interfere with cytokinesis presumably by preventing the formation of the actin-based contractile ring [5].

Biological context of Rhod

• The amino acid sequences of its effector domain is distinct from those of the other Rho family proteins, suggesting its unique cellular functions [5].
• Thus, cytoskeletal alterations including the loss of stress fibers and focal adhesions by RhoD seems to lead to the retardation of cell migration [5].
• Rac1b, a Rac1 isoform generated by alternative splicing, emerged in amniotes, and RhoD, only in therians [6].
• Furthermore, the inhibition by alendronate was reversed by geranylgeraniol, which abrogated the inhibition of Rho geranylgeranylation [7].
• The Rho-associated kinase (ROK) inhibitor Y-27632 decreased MYPT1 phosphorylation by a similar extent [8].

Anatomical context of Rhod

• Measurements of Rhod 2 fluorescence during exposure of permeabilized VM to 1000 nM [Ca2+] for 5 min confirmed that DKO myocytes have enhanced mitochondrial Ca2+ uptake, and this difference between DKO and WT myocyte mitochondria was eliminated by inhibition of NO synthesis [9].
• A Rho protein, RhoD, might provide a molecular link between membrane traffic and the cytoskeleton [3].
• Potential role of MCP-1 in endothelial cell tight junction 'opening': signaling via Rho and Rho kinase [4].
• Pharmacological blockade of caveolae or RhoA-Rho-kinase pathway was assessed by confocal microscopy in pressurized arteries to analyze protein co-localization and by co-immunoprecipitation in order to confirm protein interactions [10].
• However, inhibition of Rho signaling in combination with ectopic Rac activation rescued the corner localization of motile processes and focal adhesions [11].

Associations of Rhod with chemical compounds

• Alendronate suppresses tumor angiogenesis by inhibiting Rho activation of endothelial cells [7].
• Inhibition of the small GTPase, Rho, using C3 exoenzyme blocked lamellipodia extension entirely [11].

Analytical, diagnostic and therapeutic context of Rhod

• The complexity of the Rab and Rho GTP-binding protein subfamilies revealed by a PCR cloning approach [12].

References