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Your search keyword '"Astorga-Simón, Elsa N."' showing total 5 results
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5 results on '"Astorga-Simón, Elsa N."'

4. Architecture of the ESCPE-1 membrane coat

Author

Agencia Estatal de Investigación (España), Ministerio de Ciencia, Innovación y Universidades (España), National Institutes of Health (US), Swiss National Science Foundation, Eunice Kennedy Shriver National Institute of Child Health and Human Development (US), European Commission, Electron Biology Imaing Centre (UK), University of Leicester, López-Robles, Carlos, Scaramuzza, Stefano, Astorga-Simón, Elsa N., Ishida, Morié, Williamson, Chad D., Baños-Mateos, Soledad, Gil-Cartón, David, Romero-Durana, Miguel, Vidaurrazaga, Ander, Fernández-Recio, Juan, Rojas, Adriana L., Bonifacino, Juan S., Castaño-Díez, Daniel, Hierro, Aitor, Agencia Estatal de Investigación (España), Ministerio de Ciencia, Innovación y Universidades (España), National Institutes of Health (US), Swiss National Science Foundation, Eunice Kennedy Shriver National Institute of Child Health and Human Development (US), European Commission, Electron Biology Imaing Centre (UK), University of Leicester, López-Robles, Carlos, Scaramuzza, Stefano, Astorga-Simón, Elsa N., Ishida, Morié, Williamson, Chad D., Baños-Mateos, Soledad, Gil-Cartón, David, Romero-Durana, Miguel, Vidaurrazaga, Ander, Fernández-Recio, Juan, Rojas, Adriana L., Bonifacino, Juan S., Castaño-Díez, Daniel, and Hierro, Aitor

Abstract

Recycling of membrane proteins enables the reuse of receptors, ion channels and transporters. A key component of the recycling machinery is the endosomal sorting complex for promoting exit 1 (ESCPE-1), which rescues transmembrane proteins from the endolysosomal pathway for transport to the trans-Golgi network and the plasma membrane. This rescue entails the formation of recycling tubules through ESCPE-1 recruitment, cargo capture, coat assembly and membrane sculpting by mechanisms that remain largely unknown. Herein, we show that ESCPE-1 has a single-layer coat organization and suggest how synergistic interactions between ESCPE-1 protomers, phosphoinositides and cargo molecules result in a global arrangement of amphipathic helices to drive tubule formation. Our results thus define a key process of tubule-based endosomal sorting.

Published
2023

5. Cancer-associated mutations in VAV1 trigger variegated signaling outputs and T-cell lymphomagenesis

Author

Fundación la Caixa, Junta de Castilla y León, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Asociación Española Contra el Cáncer, Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (España), Ministerio de Educación, Cultura y Deporte (España), European Commission, Robles-Valero, Javier, Fernández-Nevado, Lucía, Lorenzo-Martín, L. Francisco, Cuadrado, Myriam, Fernández-Pisonero, Isabel, Rodríguez-Fdez, Sonia, Astorga-Simón, Elsa N., Abad, Antonio, Caloto, Rubén, Bustelo, Xosé R., Fundación la Caixa, Junta de Castilla y León, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Asociación Española Contra el Cáncer, Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (España), Ministerio de Educación, Cultura y Deporte (España), European Commission, Robles-Valero, Javier, Fernández-Nevado, Lucía, Lorenzo-Martín, L. Francisco, Cuadrado, Myriam, Fernández-Pisonero, Isabel, Rodríguez-Fdez, Sonia, Astorga-Simón, Elsa N., Abad, Antonio, Caloto, Rubén, and Bustelo, Xosé R.

Abstract

Mutations in VAV1, a gene that encodes a multifunctional protein important for lymphocytes, are found at different frequencies in peripheral T-cell lymphoma (PTCL), non-small cell lung cancer, and other tumors. However, their pathobiological significance remains unsettled. After cataloguing 51 cancer-associated VAV1 mutations, we show here that they can be classified in five subtypes according to functional impact on the three main VAV1 signaling branches, GEF-dependent activation of RAC1, GEF-independent adaptor-like, and tumor suppressor functions. These mutations target new and previously established regulatory layers of the protein, leading to quantitative and qualitative changes in VAV1 signaling output. We also demonstrate that the most frequent VAV1 mutant subtype drives PTCL formation in mice. This process requires the concurrent engagement of two downstream signaling branches that promote the chronic activation and transformation of follicular helper T cells. Collectively, these data reveal the genetic constraints associated with the lymphomagenic potential of VAV1 mutant subsets, similarities with other PTCL driver genes, and potential therapeutic vulnerabilities.

Published
2021

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