Lab presentation
The connections in our brains are constantly changing. As we interact with our environment and with each other, the connections between our neurons are remodeled so that we can retain these interactions as learning and memory. At a molecular level, the brain accomplishes this remodeling in part by making new proteins at the specific sites where our neurons interact with each other (known as synapses). Abnormalities in synaptic plasticity contribute to a wide range of neurological and cognitive disorders, such as Alzheimer’s disease, autism, schizophrenia, addiction and multiple sclerosis. The goal of our research is to understand the molecular and cellular mechanisms involved in the regulation of synaptic plasticity and dendritic branching. We use a multidisciplinary experimental approach that includes high-resolution live imaging of neurons, gene manipulation, electrophysiology experiments and multi-omics studies. We conduct many of our studies in mouse hippocampus, a structure known to be important for memory.
Keywords: Synaptic plasticity, RNA granules, splicing, local translation, intron retention, actin cytoskeleton, dendritic spines, dendritic branching, hippocampal neurons.
Projects
RNA GRANULES IN NEURONS: MOLECULAR MECHANISMS OF LOCAL CAPTURE, DISSOCIATION AND TRANSLATION
The main purpose of this project is to study the molecular mechanisms that regulate local mRNAs expression in the context of synaptic development and neuritic branching. Our purpose aims to better understand the relationship between RNA granules components and actin cytoskeleton, which is a key regulator of synaptic plasticity and dendritic morphology. To achieve this goal, we are addressing the following objectives:
1. To study RNA granule dynamics in dendrites focusing in dendritic spines and dendritic branching points.
2. To identify differential modulators of RNA granule disaggregation by interactomic analysis.
3. To study the functional relevance of candidate proteins in RNA granule entrapment and disaggregation.
ALTERNATIVE SPLICING IN NEURONAL PLASTICITY
In nervous systems, alternative splicing has emerged as a fundamental mechanism not only for the diversification of protein isoforms but also for the spatiotemporal control of transcripts. In this project we have two general goals:
1. The protein KIS is the only serine/threonine kinase that possesses a U2AF homology motif (UHM), its expression is increased over the course of embryonic development mainly in the central nervous system. Our recently proteomic analysis has shown that KIS phosphorylates numerous splicing factors. We seek to understand the function of KIS in driving neuronal specific splicing programs.
2. We are interested in investigating the possibility of local splicing in synapses and the underlying molecular mechanisms. Published data and our own results show dendritic localization of several spliceosome related proteins. We hypothesize that dendritic splicing could be an important mechanism for increasing the molecular complexity and functional capacity of the synapse.
Lab people
Carme Gallego
Principal investigator
Carme Gallego obtained her PhD degree in Biological Sciences in 1989 from the University of Barcelona. She did her postdoctoral work with Gary Johnson, studying the molecular mechanisms of cell malignancy in cancerous cells. In 1992 she joined the University of Lleida first as postdoctoral fellow and later as research associate to work on the molecular mechanisms that control the earliest steps of the cell cycle in budding yeast.
In 2000 she got a permanent position as Associated Professor starting her career as principal investigator in the field of neurobiology. From September of 2010, her group is working at IBMB where she has incorporated as Associate Scientist. Her current research is aimed at understanding the molecular mechanisms of synaptic plasticity and memory formation. As a result of the most recent work, her research group has uncovered a crosstalk mechanism that coordinates local translation and actin dynamics during dendritic spine remodeling.
Mónica Mendoza
Alba Neher Mestre
Past students
Marcos Moreno
Sara Gutiérrez
Raül Ortiz
Neus Pedraza
Marta Rafel
Serafí Cambray
Yuhui Liu
Neus Colomina
Selected publications
Mendoza MB, Gutierrez S, Ortiz R, Moreno DF, Dermit M, Dodel M, Rebollo E, Bosch M, Mardakheh FK, Gallego C. eEF1A2 controls translation and actin dynamics in dendritic spines. Sci. Signal. doi.org/10.1126/scisignal.
Yahya G, Pérez AP, Mendoza MB, Parisi E, Moreno DF, Artés MH, Gallego C*, Aldea M* (*corresponding authors). Stress granules display bistable dynamics modulated by Cdk. J Cell Biol, 220 (3) doi.org/10.1083/jcb.202005102 (2021).
Ortiz R, Georgieva MV, Gutierrez S, Pedraza N, Fernández-Moya SM, Gallego C. Recruitment of Staufen2 enhances dendritic localization of an intron-containing CaMKIIα mRNA. Cell Rep. 20(1) doi.org/10.1016/j.celrep.2017.06.026 13-20 (2017).
Georgieva MV, Yahya G, Codó L, Ortíz R, Teixidó L, Claros J, Jara R, Jara M, Iborra A, Gelpí JL, Gallego C*, Orozco M*, Aldea M*. (*corresponding authors). Inntags: small self-structured epitopes aimed at innocuous protein tagging. Nature Methods 12(10):955-8 (2015).
Pedraza N, Ortiz R, Cornadó A, Llobet A, Aldea M, Gallego C. KIS, a kinase associated with microtubule regulators, enhances translation f AMPA receptors and stimulates dendritic spine remodelling. J Neurosci, 34(42):13988-97 (2014).
All publications
Mendoza MB, Gutierrez S, Ortiz R, Moreno DF, Dermit M, Dodel M, Rebollo E, Bosch M, Mardakheh FK, Gallego C. eEF1A2 controls translation and actin dynamics in dendritic spines. Sci. Signal. doi.org/10.1126/scisignal.
Yahya G, Pérez AP, Mendoza MB, Parisi E, Moreno DF, Artés MH, Gallego C*, Aldea M* (*corresponding authors). Stress granules display bistable dynamics modulated by Cdk. J. Cell Biol., 220 (3) doi.org/10.1083/jcb.202005102 (2021).
Ortiz R, Georgieva MV, Gutierrez S, Pedraza N, Fernández-Moya SM, Gallego C. Recruitment of Staufen2 enhances dendritic localization of an intron-containing CaMKIIα mRNA. Cell Rep. 20(1) 13-20 (2017).
Georgieva MV, Yahya G, Codó L, Ortíz R, Teixidó L, Claros J, Jara R, Jara M, Iborra A, Gelpí JL, Gallego C*, Orozco M*, Aldea M*. (*corresponding authors). Inntags: small self-structured epitopes aimed at innocuous protein tagging. Nature Methods 12(10):955-8 (2015).
Pedraza N, Ortiz R, Cornadó A, Llobet A, Aldea M, Gallego C. KIS, a kinase associated with microtubule regulators, enhances translation f AMPA receptors and stimulates dendritic spine remodelling. J Neurosci, 34(42):13988-97 (2014).
Yahya G, Parisi E, Flores A, Gallego C, Aldea M. A Whi7-Anchored Loop Controls the G1 Cdk-Cyclin Complex at Start. Mol Cell, 53(1):115–126 (2014)
Ferrezuelo F, Colomina N, Palmisano A, Gari E, Gallego C, Csikasz-Nagy A, Aldea M Critical size is set at a single-cell level by growth rate to attain homeostasis and adaptation. Nat Commun , 3:1012doi:10.1038/ncomms (2012).
Asensio-Juan E; Gallego C, Martínez-BalbáS M. The histone demethylase PHF8 is essential for cytoskeleton dynamics. Nucleic Acids Res ; 40(19):9429-40 (2012).
Baba M, Keller Jr, Sun H-W, Resch W, Kuchen S, Suh HC, Hasumi H, Hasumi Y, Kieffer-Kwon K-R, Gallego C, Hughes RM, Klein ME, Oh HF, Bible P, Southon E, Tessarollo L, Schmidt LS, Linehan WM, Casellas R. “The Folliculin-Fnip1 pathway deleted in human Birt-Hogg-Dubé syndrome is required for B cell development Blood, 120(6):1254-61 (2012).
Ruiz-Miró M, Colomina N, Fernández R, Garí E, Gallego C*, Aldea M* (*corresponding authors). Translokin interacts with cyclin D1 and prevents its nuclear accumulation during cellular quiescence. Traffic 12(5):549-62 (2011).
Pedraza N, Rafel M, Navarro I, Encinas M, Aldea M, Gallego C. Mixed-Lineage Kinase 2 phosphorylates transcription factor E47 and inhibits TrkB expression to link neuronal death and survival pathways. J. Biol. Chem 284(47): 32980-8 (2009).
Cambray S, Pedraza N, Rafel M, Garí E, Aldea M, Gallego C. Protein kinase KIS localizes to RNA granules and enhances local translation. Mol Cell Biol. 29(3): 726-735 (2009).
Verges 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 to trigger cell cycle entry Mol Cell, 26(5): 649–662 (2007).
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. EMBO J. 16, 7196-7206 (1997)
Gallego C, Gupta SK, Heasley LE, Qian N, Johnson, G. Mitogen-activated protein kinase activation resulting from selective oncogene expression in NIH 3T3 and Rat 1a cells. Proc. Natl. Acad. Sci. USA 89, 7355-7359 (1992).
Gallego C, Gupta SK, Winitz S, EisfelderI BJ, Johnson GL. Myristoylation of the Gi2 polypeptide, a G protein subunit, is required for its signaling and transformation functions. Proc. Natl. Acad. Sci. USA 89, 9695-9699 (1992).
Project funding
RNA granules in neurons: Molecular mechanisms of local capture, dissociation and translation
- AGENCY: MICINN PID2020-113231GB-I00
- PERIOD: 2021-2024
- PI: Carme Gallego
Proyecto PID2020-113231GB-I00 financiado por:
Targeting mRNAs condensates in neurites for a better understanding of synaptic plasticity dysfunction in schizophrenia
Role: PI
“Fundació La Marató de TV3” Research Project, 30th Edition – Mental Health
The elongation factor eEF1A2: an emerging link between synaptic plasticity and neurological disorders
- AGENCY: MINECO BFU2017-83375-R
- PERIOD: 2018-2020
- PI: Carme Gallego
Proyecto PID2020-113231GB-I00 financiado por:
Synaptic plasticity and age at onset of psychotic disorders: molecular analysis of Neuritin
- AGENCY: Fundación Alicia Koplowitz (FAK2016)
- PERIOD: 2016-2018
- PI: Mar Fatjó-Vilas, Carme Gallego (collaborator).
Synaptic plasticity and neurological disorders: the brain elongation factor eEF1A2 isoform.
- AGENCY: MINECO BFU2014-52591-R
- PERIOD: 2015-2017
- PI: Carme Gallego.
Molecular mechanisms of neuronal plasticity: the role of KIS kinase.
- AGENCY: MICINN BFU2011-25914
- PERIOD: 2012-2014
- PI: Carme Gallego.
Plasticity and neuronal differentiation: regulation by KIS and MLK2 kinases.
- AGENCY: MICINN BFU2008-01736/BFI
- PERIOD: 2008 – 2011
- PI: Carme Gallego.
Proliferation and neuronal differentiation: opposing effects of FGF and BDNF.
- AGENCY: MEC, SAF2004-03142
- PERIOD: 2005 – 2008
- PI: Carme Gallego.
Vacancies/Jobs
If you are interested in joining the lab as postdoc or PhD student please send us your CV and cover letter: Carme Gallego cggbmc@ibmb.csic.es
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