Mecanismos moleculares de la neurosecreción

Líneas de investigación

Mecanismos moleculares de la exocitosis en un modelo neuroendocrino: la participación de proteínas del complejo de atraque vesicular y del citoesqueleto. La célula cromafin adrenomedular es uno los modelos experimentales que más ha contribuido al entendimiento del proceso exocitótico y por ello al esclarecimiento de los mecanismos moleculares de la neurotransmisión, especialmente desde que se ha demostrado la universalidad de los mecanismos y proteínas participantes en los procesos de atraque vesicular, fusión de membranas y liberación de substancias activas (hipótesis SNARE). Nuestro grupo ha venido trabajando en dos aspectos diferenciados del estudio de los mecanismos moleculares de la neurotransmisión: La implicación del binomio motor actina-miosina en el transporte vesicular acaecido durante la neurosecreción y por otro lado la determinación de los aminoácidos fundamentales para que proteínas como sinaptobrevina o SNAP-25 desarrollen su papel esencial durante la fusión de membranas. Acuñamos el término “Arquitectura molecuolar de la exocitosis” para definir la interacción de las proteínas SNARE, canales de calcio, y receptores nicotínicos (integrando con ello las líneas del Dr. Manuel Criado), con la red cortical de F-actina para con ello mejorar la eficiencia de la exocitosis.
Para ello se han desarrollado estrategias que combinan el empleo de herramientas moleculares como anticuerpos, diseño de péptidos y sobreexpresión de proteínas alteradas con técnicas biofísicas para la determinación de la neurosecreción a niveles de célula única e incluso de fusiones individuales de vesículas. Últimamente, la descripción de los mecanismos utilizados por los lípidos señal para incrementar la actividad de proteína SNARE nos a permitido vislumbrar nuevas estrategias para el tratamiento de los síndromes excitotóxicos neurodegenerativos.

Publicaciones relevantes

Acetylcholine nicotinic receptor subtypes in chromaffin cells Criado M Pflugers Arch 2018 470(1):13 https://doi.org/10.1007/s00424-017-2050-7
Emerging evidence for the modulation of exocytosis by signalling lipids Garcia-Martinez V, Gimenez-Molina Y, Villanueva J, Darios FD, Davletov B, Gutiérrez LM FEBS Lett 2018 592(21):3493 https://doi.org/10.1002/1873-3468.13178
Multiple Mechanisms Driving F-actin-Dependent Transport of Organelles to and From Secretory Sites in Bovine Chromaffin Cells Gimenez-Molina Y, Villanueva J, Frances MDM, Viniegra S, Gutiérrez LM Front Cell Neurosci 2018 12:344 https://doi.org/10.3389/fncel.2018.00344
Captivating New Roles of F-Actin Cortex in Exocytosis anc Bulk Endocytosis in Neurosecretory Cells Meunier FA, Gutierrez LM Trends Neurosci 2016 39(9):605 https://doi.org/10.1016/j.tins.2016.07.003
The position of mitochondria and ER in relation to that of the secretory sites in chromaffin cells Villanueva J, Viniegra S, Gimenez-Molina Y, Garcia-Martinez V, Exposito-Romero G, del Mar Frances M, Garcia-Sancho J, Gutierrez LM J Cell Sci 2014 127(23):5105 https://doi.org/10.1242/jcs.160242

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