Agustín D. Martínez

Cell Signalingagustin-d-martinez

Gap Junction Laboratory
Centro Interdisciplinario de Neurociencia de Valparaíso
Universidad de Valparaíso

Contact information:

E-mail: agustin.martinez at uv.cl
Teléfono: 56-32-2508415
Fax: 56-32-2508027

Laboratory Members:

Estudiates de Doctorado:
Oscar Jara Leiva (oscar.jara at cinv.cl)
Isaac García (isaac.garcia at cinv.cl)

Estudiantes de Magister:
Carolina Flores (carolina.flores at cinv.cl)
Jaime Maripillán (jaime.maripillan at cinv.cl)
Ricardo Ceriani (ricardo_ceriani at hotmail.com)
Miguel Fuentes (miguel.angel.fuentes at hotmail.com)
Jorge Castex (jorgeluiscastex at gmail.com)

Estudiantes de Pregrado:
Paula Mujica (pf.mujicacovarrubias at gmail.com)

Lab Manager y Bioquímico:
Jaime Maripillán (jaime.maripillan at cinv.cl)

Asistentes de Investigación:
Bernardo Pinto (bernardo.pinto at cinv.cl)
Pablo Gonzalez (pablo.gonzalez at cinv.cl)

 

Research overview:

Pathogenic mechanism of deafness mutations associated to Cx26. Mutations in the gene encoding Cx26 account for a large proportion of genetic deafness. These can lead to non-syndromic or syndromic disease, respectively. In syndomic deafness the hearing loss is associated with abnormal epidermal keratinisation. How these different clinical phenotypes arise remains unclear. We have study and characterized the effect of several syndromic and non-syndromic mutations in Cx26 targeting its N-termini (NT) and first transmembrane domain and using HeLa cells as exogenous expression system. All Cx26 mutants associated with non-syndromic deafness presented impairments in the function of GJCs and HCs, which parallel the severity of the disease.  But for syndromic Cx26 mutant the situation was less clear, therefore the mechanism by which Cx26 mutants induce deafness may differ from the mechanism that induces skin disease. The main goal of this work is to contribute to the understanding of the mechanism of disease associated to syndromic mutations in Cx26. This is also relevant for Cx field because we could learn more about the structural changes that control channel regulation.  For example; why a different point mutation in the same amino acid produces non-syndromic deafness (G12V) and in other case produces syndromic deafness (G12R).  These are the type of question we want to answer.

We recently obtained an ANILLO grant in association with other members of this center to study the structure and functional properties of the voltage sensor domain/s of Connexins and Pannexin channels. 

Selected Publications:

    1. B.I. Pinto, I.E. García, A. Pupo, M.A. Retamal, A.D. Martínez, R. Latorre, C. González (2016). Charged residues at the first transmembrane region mediate the voltage dependence of connexins slow gate. J. Biol. Chem. In press.
    2. A.D. Martínez, O. Jara, R. Ceriani, J. Maripillán, P. Mujica, I.E. García (2016) Methods to determinate formation of heteromeric hemichannels. In press, Book title: Gap Junction and Pannexin Channels “A Volume in the Methods in Signal Transduction Series”. Chapter 11.
    3. I.E. García, P. Prado, A. Pupo, O. Jara, D. Rojas-Gómez, P. Mujica, C. Flores-Muñoz, J. González-Casanova, C. Soto-Riveros, M. Retamal, C. González, A.D. Martínez (2016) Connexinopathies: a structural and functional glimpse. BMC-Cell Biology, In press.
    4. I.E. Garcia, F. Bosen, P. Mujica, A. Pupo, C. Flores-Muñoz, O. Jara, C. Gonzalez, K. Willecke, A.D. Martínez (2016). From Hyeperactive Connexin26 Hemichannels to Impairements in Epidermal Calcium Gradient and Permeability Barrier in Keratitis-Ichthyosis-Deafness Syndrome. Journal of Investigative Dermatology, 136:574-583. doi:10.1016/j.jid.2015.11.017. 
    5. M.A. Retamal, C.G. León, M. Ezquer, F. Ezquer, R. Del Rio, A. Pupo, A.D. Martínez, C. González (2015). Carbon Monoxide: A New Player in the Redox Regulation of Cx- Hemichannels. IUBMB life, 67(6):428-37. doi: 10.1002/iub.1388
    6. M.A. Retamal, E.P. Reyes, I.E. García, B.Pinto, A.D. Martínez, C. González (2015). Diseases associated with leaky hemichannels. Frontiers in Cellular Neuroscience. 9:267. doi: 10.3389/fncel.2015.00267.
    7. I.E. García, J. Maripillán, O. Jara, R. Ceriani, A. Palacios-Muñoz, J. Ramachandran, P. Olivero, T. Pérez-Acle, C. González, J. C. Saéz, J.E. Contreras, A.D. Martínez (2015).  Keratitis-Ichthyosis-Deafness Syndrome-Associated Cx26 Mutants Produce Nonfunctional Gap Junctions but Hyperactive Hemichannels When Co-Expressed With Wild Type Cx43. J. of Investigative Dermatology. 135(5): 1338-1347 doi: 10.1038/jid.2015.20.
    8. P. Prado-Gutierrez, A. Castro-Fariñas, L. Morgado-Rodriguez, E. Velarde-Reyes, A.D. Martínez, E. Martínez-Montes (2015). Habituation of auditory steady state responses evoked by amplitude-modulated acoustic signals in rats. Audiology Research 5(1): 113. doi: 10.4081/audiores.2015.113
    9. A. Palacios-Muñoz, M.J. Escobar, A. Vielma, J. Araya, A. Astudillo, G. Valdivia, I.E. García, J. Hurtado, O. Schmachtenberg, A.D. Martínez, A.G. Palacios (2014). Role of connexin channels in the retinal light response of a diurnal rodent. Front Cell Neurosci.  8:249. doi: 10.3389/fncel.2014.00249.
    10. F. Momboisse, M.J. Olivares, X. Báez-Matus, M.J. Guerra, C. Flores-Muñoz, J.C. Sáez, A.D. Martínez, A.M. Cárdenas (2014). Pannexin 1 channels: new actors in the regulation of catecholamine release from adrenal chromaffin cells. Front Cell Neurosci. 8:270. doi: 10.3389/fncel.2014.00270. eCollection.
    11. V.A. Figueroa, M.A. Retamal, L.A. Cea, J.D. Salas, A.A. Vargas, C.A. Verdugo, O. Jara, A.D. Martínez, J.C. Sáez (2014) Extracellular gentamicin reduces the activity of connexin hemichannels and interferes with purinergic Ca2+ signaling in HeLa cells. Front. Cell. Neurosci. 8:265. doi: 10.3389/fncel.2014.00265
    12. A.O. Ardiles, C. Flores-Muñoz, G. Toro-Ayala, A.M. Cárdenas, A.G. Palacios, P. Muñoz, M. Fuenzalida, J.C. Saez, A.D. Martinez (2014) Pannexin 1 Regulates Bidirectional Hippocampal Synaptic Plasticity in Adult Mice. Front. Cell. Neurosci. 8:326.
    13. R. Araya-Secchi, T. Perez-Acle, S. Kang, T. Huynh, A. Bernardin, Y. Escalona, J-A Garate, A. D. Martínez, I. Garcia, J.C. Sáez, R. Zhou (2014) Characterization of a novel water pocket inside the human Cx26 hemichannel structure.  Biophys J. 107(3):599-612. 
    14. A. Pupo, D. Baez-Nieto, A.D. Martínez, R. Latorre, C. González (2014) Proton channel models: Filling the gap between experimental data and the structural rationale. Channels (Austin). 8, 1–13.
    15. A.O. Ardiles, J. Ewer, M.L. Acosta, A. Kirkwood, A.D. Martinez, L. Ebensperger, F. Bozinovic, T.M. Lee, A.G. Palacios (2013). Octodon degus (Molina 1782): a model in comparative biology and biomedicine. Cold Spring Harb Protoc. 2013 Apr 1;2013(4):312-8. 
    16. P. Pastor, P. Cisternas, K. Salazar, C. Silva-Alvarez, K. Oyarce, N. Jara, F. Espinoza, A.D. Martínez, F. Nualart (2013) SVCT2 vitamin C transporter expression in progenitor cells of the postnatal neurogenic niche. Front Cell Neurosci. 7:119. 
    17. A.M. González-Jamett, F. Momboisse, M.J. Guerra, S. Ory, X Báez-Matus, N. Barraza, V. Calco, S. Houy, E. Couve, A. Neely, A.D. Martínez, S. Gasman, A.M. 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):e70638.
    18. V. Figueroa, P.J. Sáez, J.D. Salas, O. Jara, A.D. Martínez, J.C. Sáez, M.A. Retamal. (2013) Linoleic acid induces opening of connexin26 hemichannels through a PI3K/Akt/Ca(2+)-dependent pathway. Biochim Biophys Acta. 1828(3):1169-7.
    19. J.A. Orellana, A.D. Martinez, M.A. Retamal (2013). Gap junction channels and hemichannels in the CNS: Regulation by signaling molecules. Neuropharmacology 74:567-582.
    20. A.K. Schalper, M.A. Riquelme, M.C. Brañes, A.D. Martínez, J.L. Vega, V.M. Berthoud, M.V.L. Bennett, J.C. Sáez (2012) Modulation of gap junction channels and hemimchannels by growth factors.  Molecular BioSystems. 8(3):685-98.
    21. O. Jara, R. Acuña, I.E. García, J. Maripillán, V. Figueroa, J.C. Sáez, R. Araya-Secchi , C.F. Lagos, T. Pérez-Acle, V.M. Berthoud, E.C. Beyer, A.D. Martínez (2012). Critical role of the first transmembrane domain of Cx26 in regulating oligomerization and function.  Mol Biol Cell. 23(17):3299-311.
    22. F.J. Morera, A. Alioua, P. Kundu, M. Salazar, C. Gonzalez, A.D. Martinez, E. Stefani, L. Toro, R. Latorre (2012). The first transmembrane domain (TM1) of β2-subunit binds to the transmembrane domain S1 of α-subunit in BK potassium channels. FEBS Lett. 586(16):2287-93. 
    23. K.A. Schalper, M.A. Riquelme, M.C. Brañez, A.D. Martínez, J.L. Vega, V.M. Berthoud, M.V. Bennett, J.C. Sáez (2012). Modulation of gap junction channels and hemichannels by growth factors. Mol Biosyst. 8(3):685-98. 
    24. A.D. Martínez, R. Acuña, J.M., P.J. Minogue, V.M. Berthoud and E.C. Beyer (2011) Different domains are critical for oligomerization compatibility of different connexins. Biochem J. 436 (1): 35-43.
    25. A.M. González-Jamett, M. Hevia, M.J. Guerra, A.D. Martinez, A. Neely, A.M. Cárdenas (2010). The association of dynamin with synaptophysin regulates catecholamine quantal size and duration of the exocytotic events in chromaffin cells. J. Neuroscience 30: 10683-10691.
    26. A.D. Martinez, R. Acuña, V. Figueroa, J. Maripillan, B. Nicholson (2009)  Gap Junction Channels dysfunction in deafness and hearing loss. Antioxidants and Redox Signaling. 11: 309-322. 
    27. K.A. Schalper, N. Palacios-Prado, M.A. Retamal, K.F. Shoji, A.D. Martínez, and J.C. Sáez (2008). “Connexin hemichannel composition determines the FGF-1-induced membrane permeability and free [Ca2+]i responses”. Mol. Biol. Cell 19: 3501-3513.

(Financed by Millennium Institute-CINV, FONDECYT-1090573 to ADM)