Lines of investigation
Molecular mechanisms of exocytosis in a neuroendocrine model: the involvement of cytoskeleton and SNARE complex proteins:
Adrenomedullary chromaffin cells have been used as an excellent experimental model to study the exocytosis and therefore the molecular mechanisms of neurotransmission. It is now clear that the proteins involved in the processes of vesicle docking, membrane fusion and neurotransmitter release are common to many cellular systems (SNARE hypothesis). Our research interest is focused in two different aspects of the molecular mechanisms of neurotransmission: Implication of molecular motors such myosin-actin in vesicle transport during neurosecretion and the determination of essential aminoacids of synaptobrevin or SNAP-25 implicated in the process of membrane fusion. We coined the term “Molecular cytoarchitecture of exocytosis” to define the interaction between SNARE proteins, calcium channel and lately nicotinic receptors (integrating Dr. Criado main line) and the cohesive F-actin cortical network in order to improve secretory efficiency.
Experimental approaches involve strategies using antibodies, sequence peptide design and protein overexpression that demonstrate the participation of specific protein domains in exocytosis. In addition, the role of these proteins on the secretory stages have been studied using amperometry, technique that resolves single fusion events, and high resolution fluorescence microscopy. Lately, the description of the mechanisms used by signaling lipids to increase SNARE activity has allowed us to gain insights into the possible design of strategies for the treatment of excitotoxic neurodegenerative syndromes.
- 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