Rho GTPases, phosphoinositides, and actin

Croisé, Pauline; Estay-Ahumada, Catherine; Gasman, Stéphane; Ory, Stéphane

doi:10.4161/sgtp.29469

Cited by 73 publications

(40 citation statements)

References 229 publications

(252 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The dynamic remodeling of actin cytoskeleton is intimately involved in essential cellular processes such as cell adhesion and motility [ 1 ], apoptosis [ 2 ], endocytosis and phagocytosis [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Coxiella burnetii Phagocytosis Is Regulated by GTPases of the Rho Family and the RhoA Effectors mDia1 and ROCK

et al. 2015

View full text Add to dashboard Cite

The GTPases belonging to the Rho family control the actin cytoskeleton rearrangements needed for particle internalization during phagocytosis. ROCK and mDia1 are downstream effectors of RhoA, a GTPase involved in that process. Coxiella burnetii, the etiologic agent of Q fever, is internalized by the host´s cells in an actin-dependent manner. Nevertheless, the molecular mechanism involved in this process has been poorly characterized. This work analyzes the role of different GTPases of the Rho family and some downstream effectors in the internalization of C. burnetii by phagocytic and non-phagocytic cells. The internalization of C. burnetii into HeLa and RAW cells was significantly inhibited when the cells were treated with Clostridium difficile Toxin B which irreversibly inactivates members of the Rho family. In addition, the internalization was reduced in HeLa cells that overexpressed the dominant negative mutants of RhoA, Rac1 or Cdc42 or that were knocked down for the Rho GTPases. The pharmacological inhibition or the knocking down of ROCK diminished bacterium internalization. Moreover, C. burnetii was less efficiently internalized in HeLa cells overexpressing mDia1-N1, a dominant negative mutant of mDia1, while the overexpression of the constitutively active mutant mDia1-ΔN3 increased bacteria uptake. Interestingly, when HeLa and RAW cells were infected, RhoA, Rac1 and mDia1 were recruited to membrane cell fractions. Our results suggest that the GTPases of the Rho family play an important role in C. burnetii phagocytosis in both HeLa and RAW cells. Additionally, we present evidence that ROCK and mDia1, which are downstream effectors of RhoA, are involved in that process.

show abstract

Section: Introductionmentioning

confidence: 99%

Coxiella burnetii Phagocytosis Is Regulated by GTPases of the Rho Family and the RhoA Effectors mDia1 and ROCK

et al. 2015

View full text Add to dashboard Cite

show abstract

“…1 Studies in the last 2 decades have implicated Rho GTPases in most cellular processes, including cell proliferation, apoptosis, cell polarity establishment, membrane trafficking and cell migration. [2][3][4][5] Therefore, Rho GTPase signaling has been involved in many aspects of cancer biology, from tumor initiation to tumor cell proliferation, invasion and metastasis. 6,7 How Rho GTPases are modulated in tumor is currently a major and a challenging issue.…”

mentioning

confidence: 99%

Inhibition of Cdc42 and Rac1 activities in pheochromocytoma, the adrenal medulla tumor

et al. 2016

Self Cite

View full text Add to dashboard Cite

Altered Rho GTPase signaling has been linked to many types of cancer. As many small G proteins, Rho GTPases cycle between an active and inactive state thanks to specific regulators that catalyze exchange of GDP into GTP (Rho-GEF) or hydrolysis of GTP into GDP (Rho-GAP). Recent studies have shown that alteration takes place either at the level of Rho proteins themselves (expression levels, point mutations) or at the level of their regulators, mostly RhoGEFs and RhoGAPs. Most reports describe Rho GTPases gain of function that may participate to the tumorigenesis processes. In contrast, we have recently reported that decreased activities of Cdc42 and Rac1 as well as decreased expression of 2 Rho-GEFs, FARP1 and ARHGEF1, correlate with pheochromocytomas, a tumor developing in the medulla of the adrenal gland (Croise et al., Endocrine Related Cancer, 2016). Here we highlight the major evidence and further study the correlation between Rho GTPases activities and expression levels of ARHGEF1 and FARP1. Finally we also discuss how the decrease of Cdc42 and Rac1 activities may help human pheochromocytomas to develop and comment the possible relationship between FARP1, ARHGEF1 and the 2 Rho GTPases Cdc42 and Rac1 in tumorigenesis.

show abstract

“…In the developing brain, a large number of tubulin isoforms are expressed in neurons during neuronal migration and differentiation. They are globular proteins forming heterodimers that coassemble into microtubules, important cytoskeletal polymers that are involved in fundamental cellular processes such as cell division, motility, differentiation, intracellular cargo transport, and communications [44,45]. Distinct alpha-and beta-tubulin isoforms are required for the positioning, differentiation, and survival of neurons [46,47].…”

Section: Deregulated Proteins Involved In Cytoskeleton Organizationmentioning

confidence: 99%

Proteomic Analysis of Mucopolysaccharidosis IIIB Mouse Brain

et al. 2020

View full text Add to dashboard Cite

Mucopolysaccharidosis IIIB (MPS IIIB) is an inherited metabolic disease due to deficiency of α-N-Acetylglucosaminidase (NAGLU) enzyme with subsequent storage of undegraded heparan sulfate (HS). The main clinical manifestations of the disease are profound intellectual disability and neurodegeneration. A label-free quantitative proteomic approach was applied to compare the proteome profile of brains from MPS IIIB and control mice to identify altered neuropathological pathways of MPS IIIB. Proteins were identified through a bottom up analysis and 130 were significantly under-represented and 74 over-represented in MPS IIIB mouse brains compared to wild type (WT). Multiple bioinformatic analyses allowed to identify three major clusters of the differentially abundant proteins: proteins involved in cytoskeletal regulation, synaptic vesicle trafficking, and energy metabolism. The proteome profile of NAGLU−/− mouse brain could pave the way for further studies aimed at identifying novel therapeutic targets for the MPS IIIB. Data are available via ProteomeXchange with the identifier PXD017363.

show abstract

Rho GTPases, phosphoinositides, and actin

Cited by 73 publications

References 229 publications

Coxiella burnetii Phagocytosis Is Regulated by GTPases of the Rho Family and the RhoA Effectors mDia1 and ROCK

Coxiella burnetii Phagocytosis Is Regulated by GTPases of the Rho Family and the RhoA Effectors mDia1 and ROCK

Inhibition of Cdc42 and Rac1 activities in pheochromocytoma, the adrenal medulla tumor

Proteomic Analysis of Mucopolysaccharidosis IIIB Mouse Brain

Contact Info

Product

Resources

About