Cecilia Conde’research

Neurons are highly polarized cells that use various mechanisms to initiate, maintain and regulate their biological functions, having up to 10,000 times more cell surface than other cell types. To establish and maintain the different neuronal domains (somatodendritic and axonal), there are mechanisms for the delivery of specific proteins to these compartments, so that each domain has the correct molecular composition. The endosomal system participates in this complex process, specifically directing membrane components (sorting), internalizing, recycling, or degrading proteins from one domain to another, thus maintaining the complex architecture of neurons, a decisive characteristic to sustain physiological processes of neurodevelopment, including migration, polarization, and synaptic function. These processes are also highly regulated by the expression of spatiotemporally specific proteins, as well as by various extracellular signals, such as the action of TGFβ (Transforming Growth Factor), required during the development of the central and peripheral nervous system (CNS, PNS). Smad Anchor for Receptor Activation (SARA) is a signaling protein with functions in endosomal trafficking. SARA participates as a negative regulator in the TGFβ signaling pathway, regulating neuronal migration during neocortical development (CNS), while its function associated with endosomal trafficking is carried out through binding to early endosomes, participating in functions, such as the sorting and recycling of membrane proteins or in the correct distribution of endosome populations to certain neuronal compartments (Figures 1 and 2). 

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The laboratory projects propose to provide new data about physiological and pathological processes of neurodevelopment, specifically identifying and/or characterizing molecules and mechanisms that: 1) participate in the endosomal system and regulate trafficking in neurons, as well as their participation in the changes morphological observed during neuritic growth, both in the CNS and PNS; 2) regulate TGFβ signaling, allowing a successful axonal establishment and growth in the CNS and PNS; 3) regulate and/or participate in the axonal regeneration process in vitro and in vivo, in SNP; 4) participate in pathological processes, specifically, temporal lobe epilepsy. In our experiments we use cellular and molecular biology techniques, high resolution microscopy, biochemistry, and we work in murine models through neuron cultures (in vitro), or by manipulating gene expressions in the brain development of mice through electroporation technique in utero (in vivo) and in experimental models of status epilepticus.

COMPETITIVE RESEARCH FUNDS
  • 2021-2023 Transcription factors of CREB3 family: modulation of secretory pathway and implications in development and regeneration of the nervous system. National Research Council, CONICET. PI: Cecilia I. Alvarez; Co-PI: Cecilia B. Conde
  • 2021-2024. Functional analysis of SARA in newest endosomal vesicles in nervous system: potential implications on protein sorting during neurodevelopment. (PICT 2020-01268). National Agency of Science and Technology Promotion (ANPCyT-FONCyT). Argentina. PI
  • 2023-2027. Functional analysis of the SARA protein in smooth muscle cells and in a model of vascular remodeling: physiological and pathological implications. (PICT 2021-00280). National Agency of Science and Technology Promotion (ANPCyT-FONCyT). Argentina. PI: Cecilia B. Conde; Co-PI: Melina Musri.
 
PUBLICATIONS (LATEST FIVE YEARS)
  • Conde C, Bates EA, Garcia C, Lazo OM. Editorial: Neuronal cytoskeleton and GTPases in health and diseases. Front Cell Dev Biol. 2022 Sep 15;10:1025527. doi: 10.3389/fcell.2022.1025527. PMID: 36187477.
  • Capelluto DGS, Conde CB, Tumbarello DA, van den Bogaart G. Editorial: Signaling Proteins for Endosomal and Lysosomal Function. Front Cell Dev Biol. 2021 Dec 16;9:821719. doi: 10.3389/fcell.2021.821719. PMID: 34977050.
  • Urrutia PJ, Bodaleo F, Bórquez DA, Homma Y, Rozes-Salvador V, Villablanca C, Conde C, Fukuda M, González-Billault C. Tuba Activates Cdc42 during Neuronal Polarization Downstream of the Small GTPase Rab8a. J Neurosci. 2021 Feb 24;41(8):1636-1649. doi: 10.1523/JNEUROSCI.0633- 20.2020. Epub 2021 Jan 21. PMID: 33478991.
  • Rozés-Salvador V, González-Billault C, Conde C. The Recycling Endosome in Nerve Cell Development: One Rab to Rule Them All? Front Cell Dev Biol. 2020 Dec 10; 8:603794. doi: 10.3389/fcell.2020.603794. PMID: 33425908.
  • Rozés-Salvador V, Wilson C, Olmos C, Gonzalez-Billault C, Conde C. Fine-Tuning the TGFβ Signaling Pathway by SARA During Neuronal Development. Front Cell Dev Biol. 2020 Sep 3; 8:550267. doi: 10.3389/fcell.2020.550267. PMID: 33015054.
  • Siri SO, Rozés-Salvador V, de la Villarmois EA, Ghersi MS, Quassollo G, Pérez MF, Conde C. Decrease of Rab11 prevents the correct dendritic arborization, synaptic plasticity and spatial memory formation. Biochim Biophys Acta Mol Cell Res. 2020 Sep;1867(9):118735. doi: 10.1016/j.bbamcr.2020.118735. Epub 2020 May 7. PMID: 32389643.
  • Rozés-Salvador V and Conde C. (2019). Participation of Rabs during Neuronal Development and Disease. J Mol Genet Med. doi: 10.4172/1747-0862.1000397.
  • Complete and updated list available here.
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