Genetic ablation of the Rho GTPase Rnd3 triggers developmental defects in internal capsule and the globus pallidus formation

Marfull-Oromí, Pau; Fleitas, Catherine; Zammou, Bahira; Rocandio, Daniel; Ballester-Lurbe, Begoña; Terrado, José; Pérez‐Roger, Ignacio; Espinet, Carme; Egea, Joaquim

doi:10.1111/jnc.15322

Cited by 3 publications

(4 citation statements)

References 72 publications

(233 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our previous results demonstrated that Rnd3 deficient mice show alterations both in the structure and the function of the CNS (Mocholi et al, 2011;Ballester-Lurbe et al, 2015;Kaur et al, 2020;Madrigal et al, 2021;Marfull-Oromi et al, 2021). To determine if there were defects also at the subcellular level, we analyzed brain sections at the subventricular zone (SVZ) by electron microscopy (Figure 1A), where we had previously described several alterations (Ballester-Lurbe et al, 2015).…”

Section: Resultsmentioning

confidence: 99%

“…In addition, Rnd3 has an essential role in cell migration along the rostral migratory stream (RMS) and is crucial for proper olfactory bulb cell development ( Ballester-Lurbe et al, 2015 ). Finally, we have recently described that Rnd3 is necessary for the formation of dendritic spines and the corticospinal axon pathfinding as well as in the globus pallidus formation ( Kaur et al, 2020 ; Marfull-Oromi et al, 2021 ). These and other evidence point out the important role of Rnd3 in neurodevelopment, although the molecular mechanisms involved are still poorly understood.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Rnd3 Expression is Necessary to Maintain Mitochondrial Homeostasis but Dispensable for Autophagy

Cueto-Ureña

Mocholí

Escrivá-Fernández

et al. 2022

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Autophagy is a highly conserved process that mediates the targeting and degradation of intracellular components to lysosomes, contributing to the maintenance of cellular homeostasis and to obtaining energy, which ensures viability under stress conditions. Therefore, autophagy defects are common to different neurodegenerative disorders. Rnd3 belongs to the family of Rho GTPases, involved in the regulation of actin cytoskeleton dynamics and important in the modulation of cellular processes such as migration and proliferation. Murine models have shown that Rnd3 is relevant for the correct development and function of the Central Nervous System and lack of its expression produces several motor alterations and neural development impairment. However, little is known about the molecular events through which Rnd3 produces these phenotypes. Interestingly we have observed that Rnd3 deficiency correlates with the appearance of autophagy impairment profiles and irregular mitochondria. In this work, we have explored the impact of Rnd3 loss of expression in mitochondrial function and autophagy, using a Rnd3 KO CRISPR cell model. Rnd3 deficient cells show no alterations in autophagy and mitochondria turnover is not impaired. However, Rnd3 KO cells have an altered mitochondria oxidative metabolism, resembling the effect caused by oxidative stress. In fact, lack of Rnd3 expression makes these cells strictly dependent on glycolysis to obtain energy. Altogether, our results demonstrate that Rnd3 is relevant to maintain mitochondria function, suggesting a possible relationship with neurodegenerative diseases.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Rnd3 Expression is Necessary to Maintain Mitochondrial Homeostasis but Dispensable for Autophagy

Cueto-Ureña

Mocholí

Escrivá-Fernández

et al. 2022

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

show abstract

“…Rabbit anti-TH was purchased from BioLegend, catalog no. 818002 ( 84 , 85 ). Mouse anti-FLAG antibody was purchased from Sigma Aldrich, catalog no.…”

Section: Methodsmentioning

confidence: 99%

A high-affinity cocaine binding site associated with the brain acid soluble protein 1

Harraz

Malla

Semenza

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Significance Cocaine is a monoamine transport inhibitor. Current models attributing pharmacologic actions of cocaine to inhibiting the activity of the amine transporters alone failed to translate to the clinic. Cocaine inhibition of the dopamine, serotonin, and norepinephrine transporters is relatively weak, suggesting that blockade of the amine transporters alone cannot account for the actions of cocaine, especially at low doses. There is evidence for significantly more potent actions of cocaine, suggesting the existence of a high-affinity receptor(s) for the drug. Identifying and characterizing such receptors will deepen our understanding of cocaine pharmacologic actions and pave the way for therapeutic development. Here we identify a high-affinity cocaine binding site associated with BASP1 that is involved in mediating the drug’s psychotropic actions.

show abstract

“…Finally, we have recently described that Rnd3 expression in corticospinal neurons is necessary for the formation of dendritic spines and extended axons and that Rnd3 maintains the radial glial scaffold at the striatopallidal junction that facilitates corticospinal axon pathfinding (Kaur et al 2020). In addition, the absence of Rnd3 expression produces several defects in striatal and thalamocortical axonal projections as well as in the globus pallidus formation at early developmental stages (Marfull-Oromí et al 2021).…”

Section: Introductionmentioning

confidence: 99%

Rnd3 is necessary for the correct oligodendrocyte differentiation and myelination in the central nervous system

et al. 2021

View full text Add to dashboard Cite

Rho small GTPases are proteins with key roles in the development of the central nervous system. Rnd proteins are a subfamily of Rho GTPases characterized by their constitutive activity. Rnd3/RhoE is a member of this subfamily ubiquitously expressed in the CNS, whose specific functions during brain development are still not well defined. Since other Rho proteins have been linked to the myelination process, we study here the expression and function of Rnd3 in oligodendrocyte development. We have found that Rnd3 is expressed in a subset of oligodendrocyte precursor cells and of mature oligodendrocytes both in vivo and in vitro. We have analyzed the role of Rnd3 in myelination using mice lacking Rnd3 expression (Rnd3 gt/gt mice), showing that these mice exhibit hypomyelination in the brain and a reduction in the number of mature and total oligodendrocytes in the corpus callosum and striatum. The mutants display a decreased expression of several myelin proteins and a reduction in the number of myelinated axons. In addition, myelinated axons exhibit thinner myelin sheaths. In vitro experiments using Rnd3 gt/gt mutant mice showed that the differentiation of the precursor cells is altered in the absence of Rnd3 expression, suggesting that Rnd3 is directly required for the differentiation of oligodendrocytes and, in consequence, for the correct myelination of the CNS. This work shows Rnd3 as a new protein involved in oligodendrocyte maturation, opening new avenues to further study the function of Rnd3 in the development of the central nervous system and its possible involvement in demyelinating diseases.

show abstract

Genetic ablation of the Rho GTPase Rnd3 triggers developmental defects in internal capsule and the globus pallidus formation

Cited by 3 publications

References 72 publications

Rnd3 Expression is Necessary to Maintain Mitochondrial Homeostasis but Dispensable for Autophagy

Rnd3 Expression is Necessary to Maintain Mitochondrial Homeostasis but Dispensable for Autophagy

A high-affinity cocaine binding site associated with the brain acid soluble protein 1

Rnd3 is necessary for the correct oligodendrocyte differentiation and myelination in the central nervous system

Contact Info

Product

Resources

About