scholarly journals Cullin 3/KCTD5 Promotes the Ubiqutination of Rho Guanine Nucleotide Dissociation Inhibitor 1 and Regulates Its Stability

2020 ◽  
Vol 30 (10) ◽  
pp. 1488-1494
Author(s):  
Hee Jun Cho ◽  
Ki-Jun Ryu ◽  
Kyoung Eun Baek ◽  
Jeewon Lim ◽  
Taeyoung Kim ◽  
...  
Keyword(s):  
Guanine Nucleotide ◽  
Guanine Nucleotide Dissociation Inhibitor ◽  
Cullin 3

Abstract 524: Identification of Roles for the Rho-Specific Guanine Nucleotide Dissociation Inhibitor (RhoGDI) Ly-Gdi in Platelet Function

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Anh T Ngo ◽  
Marisa L Thierheimer ◽  
Özgün Babur ◽  
Anne D Rocheleau ◽  
Xiaolin Nan ◽  
...  
Keyword(s):  
Platelet Function ◽  
Rho Gtpases ◽  
Cell Biology ◽  
Rho Gtpase ◽  
Thrombus Formation ◽  
Super Resolution ◽  
Dependent Manner ◽  
Guanine Nucleotide ◽  
Morphological Alterations ◽  
Guanine Nucleotide Dissociation Inhibitor

Introduction: Upon activation, platelets undergo specific morphological alterations critical to hemostatic plug and thrombus formation via actin cytoskeletal reorganizations driven by the Rho GTPases Rac1, Cdc42 and RhoA. Here we investigate roles for Rho-specific guanine nucleotide dissociation inhibitor proteins (RhoGDIs) in regulating platelet function. Methods and Hypothesis: Through an approach combining pharmacology, cell biology and systems biology methods we assessed the hypothesis that RhoGDI proteins regulate Rho GTPase-driven platelet functions downstream of platelet integrin and glycoprotein receptors. Results: We find that platelets express two RhoGDI family members, RhoGDI and Ly-GDI. Antibody interference and platelet spreading experiments suggest a specific role for Ly-GDI in platelet function. Intracellular staining and super resolution microscopy assays find that Ly-GDI displays an asymmetric, polarized localization that largely overlaps with Rac1 and Cdc42 as well as microtubules and protein kinase C (PKC) in platelets adherent to fibrinogen. Signaling studies based on interactome and pathways analyses also support a regulatory role for Ly-GDI in platelets, as Ly-GDI is phosphorylated at PKC substrate motifs in a PKC-dependent manner in response to the platelet collagen receptor glycoprotein (GP)VI-specific agonist collagen-related peptide. Notably, inhibition of PKC diffuses the polarized organization of Ly-GDI in spread platelets relative to its colocalization with Rac1 and Cdc42. Conclusion: In conclusion, our results support roles for Ly-GDI as a localized regulator of Rho GTPases in platelets and link PKC and Rho GTPase signaling systems to platelet function.

Role of Rho-specific guanine nucleotide dissociation inhibitor α regulation in cell migration

2017 ◽  
Vol 119 (3) ◽  
pp. 183-189 ◽  
Author(s):  
Fei Xie ◽  
Shuai Shao ◽  
Aziz ur Rehman Aziz ◽  
Baohong Zhang ◽  
Hanqin Wang ◽  
...  
Keyword(s):  
Cell Migration ◽  
Guanine Nucleotide ◽  
Guanine Nucleotide Dissociation Inhibitor

scholarly journals Molecular Role for the Rab Binding Platform of Guanine Nucleotide Dissociation Inhibitor in Endoplasmic Reticulum to Golgi Transport

1998 ◽  
Vol 273 (41) ◽  
pp. 26931-26938 ◽  
Author(s):  
Shih-Kwang Wu ◽  
Peng Luan ◽  
Jeanne Matteson ◽  
Ke Zeng ◽  
Noriyuki Nishimura ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Guanine Nucleotide ◽  
Golgi Transport ◽  
Guanine Nucleotide Dissociation Inhibitor

scholarly journals Guanine nucleotide dissociation inhibitor activity of the triple GoLoco motif protein G18: alanine-to-aspartate mutation restores function to an inactive second GoLoco motif

2004 ◽  
Vol 378 (3) ◽  
pp. 801-808 ◽  
Author(s):  
Randall J. KIMPLE ◽  
Francis S. WILLARD ◽  
Melinda D. HAINS ◽  
Miller B. JONES ◽  
Gift K. NWEKE ◽  
...  
Keyword(s):  
Open Reading Frames ◽  
Guanine Nucleotide ◽  
Binding Assays ◽  
Inhibitor Activity ◽  
Ability To Act ◽  
Guanine Nucleotide Dissociation Inhibitor ◽  
Goloco Motif ◽  
Human And Mouse ◽  
Α Subunits ◽  
Reading Frames

GoLoco (‘Gαi/o–Loco’ interaction) motif proteins have recently been identified as novel GDIs (guanine nucleotide dissociation inhibitors) for heterotrimeric G-protein α subunits. G18 is a member of the mammalian GoLoco-motif gene family and was uncovered by analyses of human and mouse genomes for anonymous open-reading frames. The encoded G18 polypeptide is predicted to contain three 19-amino-acid GoLoco motifs, which have been shown in other proteins to bind Gα subunits and inhibit spontaneous nucleotide release. However, the G18 protein has thus far not been characterized biochemically. Here, we have cloned and expressed the G18 protein and assessed its ability to act as a GDI. G18 is capable of simultaneously binding more than one Gαi1 subunit. In binding assays with the non-hydrolysable GTP analogue guanosine 5´-[γ-thio]triphosphate, G18 exhibits GDI activity, slowing the exchange of GDP for GTP by Gαi1. Only the first and third GoLoco motifs within G18 are capable of interacting with Gα subunits, and these bind with low micromolar affinity only to Gαi1 in the GDP-bound form, and not to Gαo, Gαq, Gαs or Gα12. Mutation of Ala-121 to aspartate in the inactive second GoLoco motif of G18, to restore the signature acidic-glutamine-arginine tripeptide that forms critical contacts with Gα and its bound nucleotide [Kimple, Kimple, Betts, Sondek and Siderovski (2002) Nature (London) 416, 878–881], results in gain-of-function with respect to Gα binding and GDI activity.

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