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Lab presentation

Protein misfolding and accumulation of proteotoxic aggregates has a direct impact in cell aging, but the underlying molecular mechanisms are poorly understood. Although it has been mainly associated to neurodegenerative diseases, recent evidence has linked proteostasis defects to cell precursor damage in proliferative tissues.

As in many cell types of different origin, prion-like aggregates are asymmetrically distributed during cytokinesis in budding yeast, and we have found that their progressive accumulation through consecutive generations eventually inhibits cell cycle entry and leads the cell to an irreversible senescent state.

Since prion-like and proteotoxic aggregates act as chaperone sinks, our data point to the idea that chaperome alterations would mediate the observed decline in cell proliferation during cell aging. With these hypotheses we aim at the identification of key molecules and mechanisms that restrain cell proliferation during cell aging and, hence, at a better understanding of aging at a systems level.

Spatial control of cell cycle entry lab presentation

Projects

Research Lines:

  • Prions and aggregons as START inhibitors: a path to cell aging.
  • Molecular competition and cell size control.
  • Inntag: applications to the diagnostic of pathological protein-protein interactions.

Lab people

Principal investigator

After obtaining his PhD degree from the Autonomous University of Barcelona in 1982, Martí Aldea did postdoctoral work with Miguel Vicente (CSIC, Madrid) and Sidney Kushner (University of Georgia, USA), studying the mechanisms that coordinate growth and cell division in prokaryotes.

In 1992 he joined the University of Lleida as an independent scientist willing to understand how eukaryotic cells control proliferation and growth. During this period, his group discovered and deeply characterized a cytoplasmic-retention mechanism that controls the cell cycle in G1. Later work at the IBMB lead him to identify a molecular switch for cell cycle entry, and postulate a molecular theory for cell size control. As a result of the most recent work, his research group has uncovered an unexpected link between protein aggregation and cell cycle entry, pointing to proteostasis decline as a key factor causing cell proliferation decay during aging.

Selected publications

Moreno DF, Jenkins K, Morlot S, Charvin G, Csikasz-Nagy A, Aldea M. Proteostasis collapse, a hallmark of aging, hinders the chaperone-Start network and arrests cells in G1. eLife 8:e48240 (2019)


Martínez-Láinez JM, Moreno DF, Parisi E, Clotet J, Aldea M. Centromeric signaling proteins boost G1 cyclin degradation and modulate cell size in budding yeast. PLoS Biology 16:e2005388 (2018)


Parisi E, Yahya G, Flores A, Aldea M. Cdc48/p97 segregase is modulated by Cdk to determine cyclin fate during G1 progression. The EMBO Journal 37:e98724 (2018)


Saarikangas J, Caudron F, Prasad R, Moreno DF, Bolognesi A, Aldea M, Barral Y. Compartmentalization of ER-bound chaperone confines protein deposit formation to the aging yeast cell. Current Biology 27, 773–83 (2017)


Georgieva MV, Yahya G, Codó L, Ortiz R, Teixidó L, Claros J, Jara R, Jara M, Iborra A, Gelpí JL, Gallego C, Orozco M, Aldea M. Inntags: small self-structured epitopes for innocuous protein tagging. Nature Methods doi:10.1038/nmeth.3556 (2015)

All publications

Moreno DF, Jenkins K, Morlot S, Charvin G, Csikasz-Nagy A, Aldea M. Proteostasis collapse, a hallmark of aging, hinders the chaperone-Start network and arrests cells in G1. eLife 8:e48240 (2019)


Martínez-Láinez JM, Moreno DF, Parisi E, Clotet J, Aldea M. Centromeric signaling proteins boost G1 cyclin degradation and modulate cell size in budding yeast. PLoS Biology 16:e2005388 (2018)


Parisi E, Yahya G, Flores A, Aldea M. Cdc48/p97 segregase is modulated by Cdk to determine cyclin fate during G1 progression. The EMBO Journal 37:e98724 (2018)


Saarikangas J, Caudron F, Prasad R, Moreno DF, Bolognesi A, Aldea M, Barral Y. Compartmentalization of ER-bound chaperone confines protein deposit formation to the aging yeast cell. Current Biology 27, 773–83 (2017)


Georgieva MV, Yahya G, Codó L, Ortiz R, Teixidó L, Claros J, Jara R, Jara M, Iborra A, Gelpí JL, Gallego C, Orozco M, Aldea M. Inntags: small self-structured epitopes for innocuous protein tagging. Nature Methods doi:10.1038/nmeth.3556 (2015)


Yahya G, Parisi E, Flores A, Gallego C, Aldea M. A Whi7-anchored loop controls the G1 Cdk-cyclin complex at Start. Molecular Cell 53, 115-126 (2014)


Menoyo S, Ricco N, Bru S, Hernández-Ortega S, Escoté X, Aldea M, Clotet J. Phosphate-activated cyclin-dependent kinase stabilizes G1 cyclin to trigger cell cycle entry. Molecular and Cellular Biology 33, 1273-1284 (2013)


Ferrezuelo F, Colomina N, Palmisano A, Garí E, Gallego C, Csikász-Nagy A, Aldea M. The critical size is set at a single-cell level by growth rate to attain homeostasis and adaptation. Nature Communications 3, 1012 (2012)


Ruiz-Miró, M; Colomina, N; Fernández, RM; Garí, E; Gallego, C; Aldea, M. Translokin interacts with cyclin D1 and prevents its nuclear accumulation in quiescent cells. Traffic 12, 549-562 (2011)


Ferrezuelo, F; Colomina, N; Futcher, B; Aldea, M. The transcriptional network activated by Cln3 cyclin at the G1-to-S transition of the yeast cell cycle. Genome Biology 11, R67 (2010)


Cambray, S; Pedraza, N; Rafel, M; Garí, E; Aldea, M; Gallego, C. Protein kinase KIS localizes to RNA granules and enhances local translation.Molecular and Cellular Biology 29, 726-735 (2009)


Vergés, E; Colomina, N; Garí, E; Gallego, C; Aldea, M. Cyclin Cln3 is retained at the ER and released by the J-chaperone Ydj1 in late G1. Molecular Cell 26, 649-662 (2007)


Aldea, M; Colomina, N; Garí, E. Control of cell cycle and cell growth by molecular chaperones. Cell Cycle 6, 1-4 (2007, review)


Clotet, J; Escoté, X; Adrover, MA; Garí, E; Aldea, M; De Nadal, E; Posas, F. Multiple checkpoint activation by the Hog1 MAPK is required for cell survival upon osmostress. The EMBO Journal 25, 2338-2346 (2006)


Liu, Y; Encinas, M; Comella, JX; Aldea, M; Gallego, C. bHLH proteins bind to TrkB and p21Cip1 promoters linking differentiation and cell cycle arrest in neuroblastoma cells. Molecular and Cellular Biology 24, 2662-2672 (2004)


Wang, H; Garí, E; Vergés, E; Gallego, C; Aldea, M. Recruitment of Cdc28 by Whi3 restricts nuclear accumulation of the G1 cyclin-Cdk complex to late G1. The EMBO Journal 23, 180-191 (2004)


Colomina, N; Liu, Y; Aldea, M; Garí, E. TOR regulates the subcellular localization of Ime1, a transcriptional activator of meiotic development. Molecular and Cellular Biology 23, 7415-7424 (2003)


Ferrezuelo, F; Steiner, B; Aldea, M; Futcher, B. Biogenesis of yeast telomerase depends on the importin Mtr10. Molecular and Cellular Biology 22, 6046-6055 (2002)


Garí, E; Volpe, T; Wang, H; Gallego, C; Futcher, B; Aldea, M. Whi3 binds the mRNA of the G1 cyclin CLN3 to modulate cell fate in budding yeastGenes & Development 15, 2803-2808 (2001)


Colomina N, Garí E, Gallego C, Herrero E, Aldea M. G1 cyclins block the Ime1 pathway to make mitosis and meiosis incompatible in budding yeast.The EMBO Journal 18, 320-329 (1999)


Gallego C, Garí E, Colomina N, Herrero E, Aldea M. The Cln3 cyclin is downregulated by translational repression and degradation during the G1 arrest caused by nitrogen deprivation in budding yeast. The EMBO Journal 16, 7196-7206 (1997)

Project funding

Proteotoxic aggregates, chaperome alterations and cell proliferation decline during cell aging

MINECO. BFU2016-80234-R 2017-2019


Prions and aggregons as inhibitors of Start: a path to cell aging

MINECO. BFU2013-47710-R 2014-2016


Competición molecular y control del tamaño celular

MICINN BFU2010-20205/BFS 2011-2013


EpiTag: Desarrollo de nuevas etiquetas peptídicas

MICINN IPT-010000-2010-019 2011-2013


Vacancies/Jobs

We offer a PhD student position granted by the Spanish Ministry of Science and Innovation.  Applications will be considered ASAP.

Lab corner

Resources

BudJ – ImageJ plugin for budding-yeast cell analysis


CoinRICSJ – ImageJ plugin for coincidence analysis by RICS


 


Contact

Martí Aldea

Research Professor CSIC

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