The development and maintenance of neuronal polarity involves the coordination of numerous cellular events such as the assembly of actin and microtubule cytoskeleton components; the selection of membrane proteins at Golgi apparatus, the trafficking of these membrane and cytoskeleton components and the addition of membrane in sites of active growth in specialized regions of the neuron. These mechanisms are mainly regulated by the activity of various members of the small Rho GTPase family which, together with their effector proteins, control different aspects of neuronal morphology. The interest of our laboratory is to study the molecular and cellular mechanisms that regulate and integrate these events, highlighting the study of different RhoGTPases. One aim of the lab is to study the activity spatio-temporal pattern of the small Rho GTPases Rac1, Cdc42 and RhoA during early events of the pathogenesis of Alzheimer’s Disease (AD) using biosensors of activity based on the fluorescence resonance energy transfer (FRET) technique; and to evaluate how these signaling proteins contribute to the generation of alterations in the actin cytoskeleton and to the deterioration of dendritic spines during amyloid-β (Aβ42)-induced neuronal degeneration.
On the other hand, the vast majority of studies involving Rho GTPases during the generation of neuronal development and polarity have focused on this famous triad, Cdc42, Rac1 and RhoA. However, the family of small Rho GTPases harbors 20 less well-studied members, many of which are present in the nervous system and whose structural, functional and regulatory characteristics are different from the canonic members. One of this, is the GTPase RhoD, with high intrinsic GTPase activity, whose function is poorly understood especially in the nervous system, but which has unique impacts on regulation of cytoskeletal dynamics, intracellular vesicle and endosomes transport and homeostasis of the Golgi apparatus among others. Therefore, another of the laboratory’s lines of research is aimed at studying the role played by Rho GTPase RhoD during the development and generation of neuronal polarity.
COMPETITIVE RESEARCH FUNDS
- 2022. Alzheimer’s Association Research Grant to Promote Diversity (AARG-D) (AARGD-22-973030). Role of Rho GTPases during amyloid-ß induced neuronal degeneration. PI.
- 2022. Proyectos de Investigación Plurianuales 2022-2024 – Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET). “Impacto del polimorfismo Val66Met de BDNF en las propiedades ansiolíticas del ejercicio físico: mecanismos moleculares”. Investigador Grupo de Investigación.
- 2022. PICT-2020-SERIEA Grupo de Reciente Formación. (FonCyT-ANPCyT). (PICT-2020-SERIEA-02716). “RhoGTPasas atípicas durante el desarrollo neuronal: Estudio funcional de la GTPasa de ciclado rápido RhoD. PI
- 2020. IBRO Early Career Awards 2020. “Role of atypical GTPase RhoD during the development of neuronal polarity”. PI
PUBLICATIONS (LATEST FIVE YEARS)
- Rueda ES, Borgnino L, Bia G, Gil PI, Bisbal M, Pietrasiak N, Mlewski EC (2023) Responses to arsenic stress by the Andean benthic-extremophile cyanobacteria Rivularia halophile. Algal Research doi: 10.1016/j.algal.2023.103286
- Peralta Cuasolo YM, Dupraz S, Unsain N, Bisbal M, Quassollo G, Galiano MR, Grassi D, Quiroga S, Sosa LJ (2023) The GTPase Rab21 is required for neuronal development and migration in the cerebral cortex. Journal of neurochemistry. doi: 10.1111/jnc.15925
- Gastaldi L, Martín JI, Sosa LJ, Quassollo G, Peralta Cuasolo YM, Valente C, Luini A, Corda D, Cáceres A, Bisbal M (2022) BARS Influences Neuronal Development by Regulation of Post-Golgi Trafficking. Cells 11(8):1320. doi: 10.3390/cells11081320.
- Masner M, Lujea N, Bisbal M, Acosta C, and Kunda P (2021) Linoleic and Oleic acids enhance cell migration by altering the dynamics of microtubules and the remodeling of the actin cytoskeleton at the leading edge. Scientific Reports 11(1):14984. doi: 10.1038/s41598-021-94399-8.
- Pesaola F, Quassollo G, Venier, AC, De Paul, AL, Noher de Halac I, Bisbal M (2021) The Neuronal Ceroid Lipofuscinosis related protein CLN8 regulates endo-lysosomal dynamics and dendritic morphology. Biology of the Cell 113(10):419-437 doi: 10.1111/boc.202000016. *Distinguido dentro de los “top cited papers” 2021-2022 de la revista.
- Rigoni D, Avalos MP, Boezio MJ, Guzmán AS, Calfa GD, Perassi EM, Pierotti SM, Bisbal M, Garcia-Keller C, Cancela LM, Bollati F. (2021) Stress-induced vulnerability to develop cocaine addiction depends on cofilin modulation. Neurobiology of the Stress 15:100349 eCollection 2021. doi: 10.1016/j.ynstr.2021.100349
- Morales C, Bisbal M, Bollo M. (2021) Molecular Modulation by Lentivirus-Delivered Specific shRNAs in Endoplasmic Reticulum Stressed Neurons. JoVe Journal 170 doi: 10.3791/61974.
- Martínez GF, Gazal NG, Quassollo G, Szalai AM, Cid-Pellitero ED, Durcan TM, Fon EA, Bisbal M, Stefani FD, Unsain N. (2020) Quantitative expansion microscopy for the characterization of the spectrin periodic skeleton of axons using fluorescence microscopy. Scientific reports 10(1):2917. doi: 10.1038/s41598-020-59856-w.
- Bisbal M*, Sanchez M*. (2019) Neurotoxicity of the Pesticide Rotenone on neuronal polarization: a mechanistic approach. Neural regeneration research 14:762-6. doi: 10.4103/1673-5374.249847. (*co-corresponding authors).
- Complete and updated list available here.
