Line 2: Cellular signaling.
This line studies the molecular mechanisms of intercellular signaling pathways that are crucial for the proper functioning of various systems such as the nervous system. The work focuses on the molecular structures formed by connexins and pannexins and alterations, which can cause deafness as well as alterations that develop in neuroinflammation in various neurodegenerative diseases and diseases that affect behavior. They evaluate how various pathological conditions affect synaptic plasticity processes, neuronal excitability, neurosecretion and postsynaptic responses. In addition, the role of proteins involved in neurosecretion such as dynamin-2 and whose alterations affect the intracellular transport of the proteins necessary for the metabolism of postsynaptic cells is studied. Cell cultures and various in vivo systems are used (e.g., transgenic mice, Drosophila melanogaster fly, and unicellular organisms) and molecular, electrophysiological, fluorescence microscopy, and molecular dynamics techniques are applied.
Researchers.
Juan Carlos Sáez (Director Alterno CINV) / fono:(56) 2 3542862 / jsaez@bio.puc.cl
Ana María Cárdenas / fono:(56) 32 2508052 / ana.cardenas@uv.cl
Agustín Martínez / fono:(56) 32 2508415 / agustin.martinez@uv.cl
Helmuth Sánchez / fono:(56) 32 2508023 / helmuth.sanchez@cinv.cl
Arlek González / fono:(56) 32 2508022 / arlek.gonzalez@cinv.cl
Associate Researchers.
Postdoctoral Researchers.
Iván Bravo / fono:(56) 32 2508160 / ivan.bravo@cinv.cl
Paloma Harcha / fono: (56) 2 3542860 / paharcha@gmail.com
Nicolás Palacios-Prado / fono: (56) 32 2508160 / n.palacios.prado@gmail.com
Magdiel A. Salgado / fono: (56) 32 2508160 / magsalgado@udec.cl
PhD Students.
Juan Güiza / fono:(56) 32 2508157 / juan.igh@hotmail.com
Carolina Flores / fono:(56) 32 2508023 / carolina.flores@cinv.cl
Claudia García / fono: (56) 32 2508160 / claudia.g.r@hotmail.com
Joel Novoa (Magister) / fono: (56) 32 2508023 / joel.novoa.m@gmail.com
Daniela Ponce (Magister) / dponcelopez93@gmail.com
Jorge Arriagada Díaz (Magister) / j.arriagada.diaz@gmail.com
Lorena Prado Vega (Magister) / lorena.prado.vega@gmail.com
- Giaume C., Naus C, Sáez JC, Leybaert L. Glial connexins and pannexins in healthy and diseased brain. Physiol Rev. 2021: 101(1):93-145. doi: 10.1152/physrev.00043.2018
- Cisterna CB., Vargas A.A., Puebla C., Lagos C.F., Escamilla R., Matus M-F., Vilos C., Cea L.A., Barnafi E., Gaete H., Escobar D.F., Cardozo C., Sáez J.C. Active acetylcholine receptors prevent the atrophy of skeletal muscles and favor reinnervation. Nature Comm. 11: 1073, (2020). doi: 10.1038/s41467-019-14063-8.
- Arriagada-Diaz J, Prado-Vega L, Cárdenas Díaz AM, Ardiles AO, Gonzalez-Jamett AM (2020) Dynamin Superfamily at Pre- and Postsynapses: Master Regulators of Synaptic Transmission and Plasticity in Health and Disease. Neuroscientist. 2020 Dec 10:1073858420974313. doi: 10.1177/1073858420974313.
- García IE, Villanelo F, Contreras GF, Pupo A, Pinto BI, Contreras JE, Pérez-Acle T, Alvarez O, Latorre R, Martínez AD, González C (2018). The syndromic deafness mutation G12R impairs fast and slow gating in Cx26 hemichannels. J Gen Physiol. 150(5):697-711. doi: 10.1085/jgp.201711782.
- González-Jamett AM, Baez-Matus X, Olivares MJ, Hinostroza F, Guerra-Fernández MJ, Vasquez-Navarrete J, Thao Bui M, Guicheney P, Romero NB, Bevilacqua JA, Bitoun M, Caviedes P, Cárdenas AM. (2017). Dynamin-2 mutations linked to Centronuclear Myopathy impair actin-dependent trafficking in muscle cells. Scientific Reports. 7(1):4580 doi: 10.1038/s41598-017-04418-w
- González-Jamett AM , Guerra MJ , Olivares MJ , Haro-Acuña V , Baéz-Matus X , Vásquez-Navarrete J, Momboisse F , Martinez-Quiles N, Cárdenas AM. (2017). The F-Actin Binding Protein Cortactin Regulates the Dynamics of the Exocytotic Fusion Pore through its SH3 Domain. Front. Cell. Neurosci., doi: 10.3389 /fnc el.2017.00130
- García IE, Bosen F, Mujica P, Pupo A, Flores-Muñoz C, Jara O, Gonzalez C, Willecke K and Martinez AD (2016) From Hyperactive Connexin26 Hemichannels to Impairments in Epidermal Calcium Gradient and Permeability Barrier in the Keratitis-Ichthyosis-Deafness Syndrome. J Invest Dermatol 136(3):574-83. doi: 10.1016/j.jid.2015.11.017.
- Harcha PA, Vargas A, Yi C, Koulakoff AA, Giaume C, Sáez JC.Hemichannels Are Required for Amyloid β-Peptide-Induced Degranulation and Are Activated in Brain Mast Cells of APPswe/PS1dE9 Mice. J Neurosci. 2015 Jun 24;35(25):9526-38. doi: 10.1523/JNEUROSCI.3686-14.2015.
- García IE, Maripillán J, Jara O, Ceriani R, Palacios-Muñoz A, Ramachandran J, Olivero P, Pérez-Acle T, González C, Sáez JC, Contreras JE, Martínez AD (2015). Keratitisichthyosis-deafness syndrome-associated Cx26 mutants produce nonfunctional gap junctions but hyperactive hemichannels when co-expressed with wild type Cx43. J Invest Dermatol 135(5): 1338-47. doi: 10.1038/jid.2015.20.
- González-Jamett AM, Momboisse F, Guerra MJ, Ory S, Báez-Matus X, Barraza N, Calco V, Houy S, Couve E, Neely A, Martínez AD, Gasman S, Cárdenas AM (2013). Dynamin-2 regulates fusion pore expansion and quantal release through a mechanism that involves actin dynamics in neuroendocrine chromaffin cells. PLoS One 8(8):70638. doi: 10.1371/journal.pone.0070638.
- Cea LC, Cisterna BA, Puebla C, Frank M, Figueroa XF, Cardozo C, Willecke K, Latorre R, Sáez JC (2013). De novo expression of connexin hemichannels in denervated fast skeletal muscles leads to atrophy. Proc Natl Acad Sci USA 110(40):16229-16234. doi: 10.1073/pnas.1312331110.
- Jara O, Acuña R, García IE, Maripillán J, Figueroa V, Sáez JC, Araya-Secchi R, Lagos CF, Perez-Acle T, Berthoud VM, Beyer EC, Martínez AD (2012). Critical role of the first transmembrane domain of Cx26 in regulating oligomerization and function. Mol Biol Cell 23(17):3299-3311. doi: 10.1091/mbc.E11-12-1058.
Ongoing projects.
Instituto Milenio-CINV
Año: 2016-2021
Concurso: Proyectos Institutos Milenio 2009 – ICM09-022-P
Financiamiento: Ministerio de Economía, Fomento y Turismo de Chile
Investigador Principal: Ramón Latorre
Otros Investigadores: Juan Carlos Sáez, Alan Neely, Ana María Cárdenas, John Ewer, Kathleen Whitlock, Adrián Palacios, Tomás Pérez-Acle, David Naranjo, Fernando González-Nilo, Oliver Schmachtenberg, Agustín Martínez, Patricio Orio, Andrés Chávez, Pablo Moya, Andrea Calixto, Carlos González.
Otras Universidades o Instituciones: Centro Interdisciplinario de Neurociencia de Valparaíso, Pontificia Universidad Católica, Universidad Andrés Bello, Fundación Ciencia y Vida.
CONICYT
MOLECULAR MECHANISMS OF CONNEXIN HEMICHANNEL HYPERACTIVITY IN KID (KERATITIS-ICHTHYOSIS-DEAFNESS) SYNDROME
Año: abril 2017 – abril 2020
Concurso: Fondecyt Regular 2017 – # 1171240
Financiamiento: Conicyt
Investigador Principal: Agustín Martínez
Otros Investigadores: John Ewer
IS THERE A VOLTAGE-CONTROLLED HYDRAULIC GATING IN THE HUMAN CONNEXIN 26 HEMICHANNEL?
Años: marzo 2016 – marzo 2020
Concurso: Fondecyt Regular 2016 – # 1160574
Financiamiento: Conicyt
Investigador Principal: Tomás Pérez-Acle
Otros Investigadores: Agustín Martínez
ROLE OF DYSFERLIN IN CYTOSKELETAL ACTIN REMODELING AND ITS IMPACT ON VESICLE TRAFFICKING AND MEMBRANE REPAIR IN MUSCULAR DYSTROPHY LINKED TO DYSFERLIN MUTATIONS
Año: 1 abril 2016 – 1 abril 2020
Concurso: Fondecyt Regular 2016 – # 1160495
Financiamiento: Conicyt
Investigador Principal: Ana María Cárdenas
Otros Investigadores: Pablo Caviedes
Otras Universidades o Instituciones: Universidad de Chile
NEURONAL DERIVED FACTOR(S) AND MECHANISM(S) THAT REPRESS THE EXPRESSION OF NONSELECTIVE ION CHANNELS IN NORMAL ADULT SKELETAL MUSCLES
Año: marzo 2015 – marzo 2019
Concurso: Fondecyt Regular 2015 – #° 1150291
Financiamiento: Conicyt
Investigador Principal: Juan Carlos Sáez
Coinvestigador(es): Bruno Cisterna, Rosalba Escamilla, Carlos Puebla
Instituciones coinvestigador(es): Pontificia Universidad Católica de Chile
CONNEXIN HEMICHANNELS AS MEDIATORS OF SARCOLEMMAL AND MITOCHONDRIAL DYSFUNCTION IN RESPIRATORY AND PERIPHERAL MUSCLE IN THE PATHOGENESIS OF SEPSIS ASSOCIATED-INTENSIVE CARE UNIT ACQUIRED WEAKNESS (ICUAW)
Año: marzo 2014 – marzo 2018
Concurso: Fondecyt Regular 2014 – # 1141092
Financiamiento: Conicyt
Investigador Principal: Tomas Regueira Heskia
Otros Investigadores: Juan Carlos Sáez, Anibal Vargas, Luis Cea
Otras Universidades o Instituciones: Pontificia Universidad Católica de Chile
