Rho-family GTPases: it's not only Rac and Rho (and I like it)

Wennerberg, Krister; Der, Channing J.

doi:10.1242/jcs.01118

Cited by 534 publications

(527 citation statements)

References 115 publications

Supporting

Mentioning

496

Contrasting

Unclassified

Order By: Relevance

“…RhoB is an attractive candidate for this effect, because it is both farnesylated and geranylgeranylated (76) and it plays a known role in the phagocytosis of Pneumocystis (77). Whether farnesyltransferase inhibitors also shift the balance toward production of other geranylgeranylated proteins that could enhance efferocytosis, like Rac-1, Cdc42, or RhoG (43,78), remains to be determined.…”

Section: Discussionmentioning

confidence: 99%

Lovastatin Enhances Clearance of Apoptotic Cells (Efferocytosis) with Implications for Chronic Obstructive Pulmonary Disease

Morimoto

Janssen²,

Fessler³

et al. 2006

The Journal of Immunology

201

179

View full text Add to dashboard Cite

Statins are potent, cholesterol-lowering agents with newly appreciated, broad anti-inflammatory properties, largely based upon their ability to block the prenylation of Rho GTPases, including RhoA. Because phagocytosis of apoptotic cells (efferocytosis) is a pivotal regulator of inflammation, which is inhibited by RhoA, we sought to determine whether statins enhanced efferocytosis. The effect of lovastatin on efferocytosis was investigated in primary human macrophages, in the murine lung, and in human alveolar macrophages taken from patients with chronic obstructive pulmonary disease. In this study, we show that lovastatin increased efferocytosis in vitro in an 3-hydroxyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase-dependent manner. Lovastatin acted by inhibiting both geranylgeranylation and farnesylation, and not by altering expression of key uptake receptors or by increasing binding of apoptotic cells to phagocytes. Lovastatin appeared to exert its positive effect on efferocytosis by inhibiting RhoA, because it 1) decreased membrane localization of RhoA, to a greater extent than Rac-1, and 2) prevented impaired efferocytosis by lysophosphatidic acid, a potent inducer of RhoA. Finally, lovastatin increased efferocytosis in the naive murine lung and ex vivo in chronic obstructive pulmonary disease alveolar macrophages in an HMG-CoA reductase-dependent manner. These findings indicate that statins enhance efferocytosis in vitro and in vivo, and suggest that they may play an important therapeutic role in diseases where efferocytosis is impaired and inflammation is dysregulated.

show abstract

Section: Discussionmentioning

confidence: 99%

Lovastatin Enhances Clearance of Apoptotic Cells (Efferocytosis) with Implications for Chronic Obstructive Pulmonary Disease

Morimoto

Janssen²,

Fessler³

et al. 2006

The Journal of Immunology

201

179

View full text Add to dashboard Cite

show abstract

“…The Rho subfamily consists of more than 20 members, which share 50% sequence identity and are ubiquitously expressed (Ridley 2000;Wennerberg and Der 2004). After binding of GTP Rho proteins are in the active conformation and inactive when bound to GDP (Fig.…”

Section: The Targets Of C3-like Exoenzymes Are Molecular Switchesmentioning

confidence: 99%

“…Rho proteins are master regulators of the actin cytoskeleton (Burridge and Wennerberg 2004;Hall 1998). Moreover, they are involved in cell and smooth muscle contraction, phagocytosis, polarity, activation of transcription, cell cycle progression and cell transformation (Bishop and Hall 2000;Etienne-Manneville and Hall 2002;Jaffe and Hall 2002;Wennerberg and Der 2004). The signal transduction of Rho is terminated by intrinsic hydrolysis of Rho-GTP, which is catalyzed by GTPase activating proteins (GAPs).…”

Section: The Targets Of C3-like Exoenzymes Are Molecular Switchesmentioning

confidence: 99%

C3 exoenzymes, novel insights into structure and action of Rho-ADP-ribosylating toxins

Vogelsgesang

Pautsch

Aktories

2006

Naunyn-Schmied Arch Pharmacol

102

View full text Add to dashboard Cite

The family of C3-like exoenzymes comprises seven bacterial ADP-ribosyltransferases of different origin. The common hallmark of these exoenzymes is the selective N-ADP-ribosylation of the low molecular mass GTPbinding proteins RhoA, B, and C and inhibition of signal pathways controlled by Rho GTPases. Therefore, C3-like exoenzymes were applied as pharmacological tools for analyses of cellular functions of Rho protein in numerous studies. Recent structural and functional analyses of C3-like exoenzymes provide detailed information on the molecular mechanisms and functional consequences of ADP-ribosylation catalyzed by these toxins. More recently additional non-enzymatic actions of C3-like ADP-ribosyltransferases have been identified showing that C3 transferases from Clostridium botulinum and Clostridium limosum form a GDI-like complex with the Ras-like low molecular mass GTPase Ral without ADP-ribosylation. These results add novel information on the molecular mode of action(s) of C3-like exoenzymes and are discussed in this review.

show abstract

“…15 The RhoA subfamily consists of RhoA, RhoB and RhoC, which exhibit approximately 85% amino acid sequence identity. 15,16 RhoB, contrary to RhoA and RhoC, is generally regarded as a tumor suppressor protein. 17 RhoB protein can be either geranylgeranylated (RhoB-GG) or farnesylated (RhoB-F) 18 and this may affect its intracellular localization (reviewed in 17 ).…”

Section: Introductionmentioning

confidence: 99%

RhoB is a component of the human cytomegalovirus assembly complex and is required for efficient viral production

et al. 2015

View full text Add to dashboard Cite

Human Cytomegalovirus (HCMV), an ubiquitous b-herpesvirus, is a significant pathogen that causes medically severe diseases in immunocompromised individuals and in congenitally infected neonates. RhoB belongs to the family of Rho GTPases, which regulates diverse cellular processes. Rho proteins are implicated in the entry and egress from the host cell of mainly a-and g-herpesviruses, whereas b-herpesviruses are the least studied in this regard. Here, we studied the role of RhoB GTPase during HCMV lytic infection. Microscopy analysis, both in fixed and live infected cells showed that RhoB was translocated to the assembly complex/compartment (AC) of HCMV, a cytoplasmic zone in infected cells where many viral structural proteins are known to accumulate and assembly of new virions takes place. Furthermore, RhoB was localized at the AC even when the expression of the late HCMV AC proteins was inhibited. At the very late stages of infection, cellular projections were formed containing RhoB and HCMV virions, potentially contributing to the successful viral spread. Interestingly, the knockdown of RhoB in HCMV-infected cells resulted in a significant reduction of the virus titer and could also affect the accumulation of AC viral proteins at this subcellular compartment. RhoB knockdown also affected actin fibers' structure. Actin reorganization was observed at late stages of infection originating from the viral AC and surrounding the cellular projections, implying a potential interplay between RhoB and actin during HCMV assembly and egress. In conclusion, our results demonstrate for the first time that RhoB is a constituent of the viral AC and is required for HCMV productive infection.

show abstract

Rho-family GTPases: it's not only Rac and Rho (and I like it)

Cited by 534 publications

References 115 publications

Lovastatin Enhances Clearance of Apoptotic Cells (Efferocytosis) with Implications for Chronic Obstructive Pulmonary Disease

Lovastatin Enhances Clearance of Apoptotic Cells (Efferocytosis) with Implications for Chronic Obstructive Pulmonary Disease

C3 exoenzymes, novel insights into structure and action of Rho-ADP-ribosylating toxins

RhoB is a component of the human cytomegalovirus assembly complex and is required for efficient viral production

Contact Info

Product

Resources

About