A5022818255- Cellular transport and secretion
- Neuroscience and Neuropharmacology Research
- Connexins and lens biology
- Ion channel regulation and function
- Lipid Membrane Structure and Behavior
- Microtubule and mitosis dynamics
- Muscle Physiology and Disorders
- Genetic Neurodegenerative Diseases
- Cardiomyopathy and Myosin Studies
- Down syndrome and intellectual disability research
- Advanced Fluorescence Microscopy Techniques
- Cellular Mechanics and Interactions
- Signaling Pathways in Disease
- Retinal Development and Disorders
- Erythrocyte Function and Pathophysiology
- Biochemical effects in animals
- RNA regulation and disease
- Photoreceptor and optogenetics research
- Endoplasmic Reticulum Stress and Disease
- Adipose Tissue and Metabolism
- Mitochondrial Function and Pathology
- Calcium signaling and nucleotide metabolism
- Nicotinic Acetylcholine Receptors Study
- Adenosine and Purinergic Signaling
- Flavonoids in Medical Research
University of Valparaíso
2016-2025
Valparaiso University
2010-2022
University of Chile
2018
Clínica MEDS (Chile)
2017
Hospital Clínico de la Universidad de Chile
2016
Over the past years, dynamin has been implicated in tuning amount and nature of transmitter released during exocytosis. However, mechanism involved remains poorly understood. Here, using bovine adrenal chromaffin cells, we investigated whether this rely on dynamin’s ability to remodel actin cytoskeleton. According idea, inhibition GTPase activity suppressed calcium-dependent de novo cortical altered network. Similarly, expression a small interfering RNA directed against dynamin-2, an isoform...
Although synaptophysin is one of the most abundant integral proteins synaptic vesicle membranes, its contribution to neurotransmitter release remains unclear. One possibility that through association with dynamin it controls fine tuning transmitter release. To test this hypothesis, we took advantage amperometric measurements quantal catecholamine from chromaffin cells. First, showed and interact in granule-rich fractions interaction relies on C terminal synaptophysin. Experimental maneuvers...
Abstract Dynamin-2 is a ubiquitously expressed GTP-ase that mediates membrane remodeling. Recent findings indicate dynamin-2 also regulates actin dynamics. Mutations in cause dominant centronuclear myopathy (CNM), congenital characterized by progressive weakness and atrophy of skeletal muscles. However, the muscle-specific roles affected these mutations remain elusive. Here we show that, muscle cells, activity involved de novo polymerization as well actin-mediated trafficking glucose...
Long-term potentiation (LTP) and long-term depression (LTD) are two forms of synaptic plasticity that have been considered as the cellular substrate memory formation. Although LTP has received considerable more attention, recent evidences indicate LTD plays also important roles in acquisition storage novel information brain. Pannexin 1 (Panx1) is a membrane protein non-selective channels which shown to modulate induction hippocampal plasticity. Animals lacking Panx1 or blockade precludes...
Objective Autosomal dominant centronuclear myopathy (AD-CNM) is a neuromuscular congenital disease caused by mutations in the DNM2 gene that encodes dynamin-2 (DNM2). The main clinical features of AD-CNM are progressive weakness and atrophy skeletal muscles. However, cognitive defects have also been reported, suggesting AD-CNM-causing might affect central nervous system (CNS). We recently demonstrated excitatory synaptic transmission occur brain transgenic knock-in (KI) mice harboring...
Synaptic loss induced by soluble oligomeric forms of the amyloid β peptide (sAβos) is one earliest events in Alzheimer´s disease (AD) and thought to be major cause cognitive deficits. These abnormalities rely on defects synaptic plasticity, a series manifested as activity-dependent modifications structure function. It has been reported that Pannexin1 (Panx1), non-selective channel implicated cell communication intracellular signaling, modulates induction excitatory plasticity under...
The cortical actin network is dynamically rearranged during secretory processes. Nevertheless, it unclear how de novo polymerization and the disruption of preexisting control transmitter release. Here we show that in bovine adrenal chromaffin cells, both formation new filaments are induced by Ca2+ concentrations trigger exocytosis. These two processes appear to regulate different stages exocytosis; whereas inhibition with N-WASP inhibitor wiskostatin restricts fusion pore expansion, thus...
Enhanced activity and overexpression of Pannexin 1 (Panx1) channels contribute to neuronal pathologies such as epilepsy Alzheimer’s disease (AD). The Panx1 channel ablation alters the hippocampus’s glutamatergic neurotransmission, synaptic plasticity, memory flexibility. Nevertheless, Panx1-knockout (Panx1-KO) mice still retain ability learn, suggesting that compensatory mechanisms stabilize their activity. Here, we show absence in adult brain promotes a series structural functional...
Upon cell stimulation, the network of cortical actin filaments is rearranged to facilitate neurosecretory process. This rearrangement includes both disruption preexisting and de novo polymerization. However, mechanism by which a Ca2+ signal elicits formation new remains uncertain. Cortactin, an actin-binding protein that promotes polymerization in synergy with nucleation promoting factor N-WASP, could play key role this mechanism. We addressed hypothesis analyzing exocytosis bovine adrenal...
Abstract Aims Dynamin‐2 is a large GTPase, member of the dynamin superfamily that regulates membrane remodelling and cytoskeleton dynamics. Mutations in dynamin‐2 gene ( DNM2 ) cause autosomal dominant centronuclear myopathy (CNM), congenital neuromuscular disorder characterised by progressive weakness atrophy skeletal muscles. Cognitive defects have been reported some ‐linked CNM patients suggesting these mutations can also affect central nervous system (CNS). Here we studied how...
Abstract Dynamins are large GTPases whose primary function is not only to catalyze membrane scission during endocytosis but also modulate other cellular processes, such as actin polymerization and vesicle trafficking. Recently, we reported that centronuclear myopathy associated dynamin‐2 mutations, p.A618T, p.S619L, impair Ca 2+ ‐induced exocytosis of the glucose transporter GLUT4 containing vesicles in immortalized human myoblasts. As occur within rapid timescales, here applied...
Abstract Various studies have focused in the relative contribution of different voltage‐activated Ca 2+ channels (VACC) to total transmitter release. However, how entry through a given VACC subtype defines pattern individual exocytotic events remains unknown. To address this question, we used amperometry bovine chromaffin cells. L, N, and P/Q were individually or jointly blocked with furnidipine, ω‐conotoxin GVIA, ω‐agatoxin IVA, MVIIC. The three channel types contributed similarly cytosolic...
Under basal conditions the action potential firing rate of adrenal chromaffin cells is lower than 0.5 Hz. The maintenance secretory response at such frequencies requires a continuous replenishment releasable vesicles. However, mechanism that allows vesicle remains unclear. Here, using membrane capacitance measurements on mouse cells, we studied group vesicles released by single potential-like stimulus (APls). exocytosis triggered APls (ETAP) represents fraction (40%) immediately pool, highly...
Dysferlin is a transmembrane C-2 domain-containing protein involved in vesicle trafficking and membrane remodeling skeletal muscle cells. However, the mechanism by which dysferlin regulates these cellular processes remains unclear. Since actin dynamics critical for remodeling, we studied role of Ca2+-induced G-actin incorporation into filaments four different immortalized myoblast cell lines (DYSF2, DYSF3, AB320, ER) derived from patients harboring mutations gene. As compared with myoblasts...
Gain-of-function mutations of dynamin-2, a mechano-GTPase that remodels membrane and actin filaments, cause centronuclear myopathy (CNM), congenital disease mainly affects skeletal muscle tissue. Among these mutations, the variants p.A618T p.S619L lead to gain function severe neonatal phenotype. By using total internal reflection fluorescence microscopy (TIRFM) in immortalized human myoblasts expressing pH-sensitive fluorescent protein (pHluorin) fused insulin-responsive aminopeptidase IRAP...
Abstract β‐Subunits of the Ca 2+ channel have been conventionally regarded as auxiliary subunits that regulate expression and activity pore‐forming α 1 subunit. However, they comprise protein–protein interaction domains, such a SRC homology 3 domain (SH3) domain, which make them potential signaling molecules. Here we evaluated role β2a subunit channels (Ca V β2a) its SH3 (β2a‐SH3) in late stages trafficking bovine adrenal chromaffin cells. Cultured cells were injected with or β2a‐SH3 under...