99 research outputs found
Lobe Specific Ca2+-Calmodulin Nano-Domain in Neuronal Spines: A Single Molecule Level Analysis
Calmodulin (CaM) is a ubiquitous Ca2+ buffer and second messenger that affects cellular function as diverse as cardiac excitability, synaptic plasticity, and gene transcription. In CA1 pyramidal neurons, CaM regulates two opposing Ca2+-dependent processes that underlie memory formation: long-term potentiation (LTP) and long-term depression (LTD). Induction of LTP and LTD require activation of Ca2+-CaM-dependent enzymes: Ca2+/CaM-dependent kinase II (CaMKII) and calcineurin, respectively. Yet, it remains unclear as to how Ca2+ and CaM produce these two opposing effects, LTP and LTD. CaM binds 4 Ca2+ ions: two in its N-terminal lobe and two in its C-terminal lobe. Experimental studies have shown that the N- and C-terminal lobes of CaM have different binding kinetics toward Ca2+ and its downstream targets. This may suggest that each lobe of CaM differentially responds to Ca2+ signal patterns. Here, we use a novel event-driven particle-based Monte Carlo simulation and statistical point pattern analysis to explore the spatial and temporal dynamics of lobe-specific Ca2+-CaM interaction at the single molecule level. We show that the N-lobe of CaM, but not the C-lobe, exhibits a nano-scale domain of activation that is highly sensitive to the location of Ca2+ channels, and to the microscopic injection rate of Ca2+ ions. We also demonstrate that Ca2+ saturation takes place via two different pathways depending on the Ca2+ injection rate, one dominated by the N-terminal lobe, and the other one by the C-terminal lobe. Taken together, these results suggest that the two lobes of CaM function as distinct Ca2+ sensors that can differentially transduce Ca2+ influx to downstream targets. We discuss a possible role of the N-terminal lobe-specific Ca2+-CaM nano-domain in CaMKII activation required for the induction of synaptic plasticity
Fish passage design for sustainable hydropower in the temperate Southern Hemisphere:An evidence review
Cue reactivity and its relation to craving and relapse in alcohol dependence: a combined laboratory and field study
Screening and concurrent brief intervention of conjoint hazardous or harmful alcohol and tobacco use in hospital out-patients in Thailand: a randomized controlled trial
A scoping review and thematic analysis of social and behavioural research among HIV-serodiscordant couples in high-income settings.
CAPRISA, 2015.Abstract available in pdf
Management of chronic pain with chronic opioid therapy in patients with substance use disorders
Neuroendocrine, Psychophysiological and Subjective Reactivity to an Alcohol Placebo in Male Alcoholic Patients
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65338/1/j.1530-0277.1987.tb01311.x.pd
Biomethylation and biotransformation of arsenic in a freshwater food chain: Green alga (chlorella vulgaris)?shrimp (neocaridina denticulata)?killifish (oryzias iatipes)
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