Unique patterns of transcript and miRNA expression in the South American strong voltage electric eel (Electrophorus electricus).

Background: With its unique ability to produce high-voltage electric discharges in excess of 600 volts, the South American strong voltage electric eel (Electrophorus electricus) has played an important role in the history of science. Remarkably little is understood about the molecular nature of its electric organs.

Results: We present an in-depth analysis of the genome of E.

Nonhuman genetics. Genomic basis for the convergent evolution of electric organs.

Little is known about the genetic basis of convergent traits that originate repeatedly over broad taxonomic scales. The myogenic electric organ has evolved six times in fishes to produce electric fields used in communication, navigation, predation, or defense. We have examined the genomic basis of the convergent anatomical and physiological origins of these organs by assembling the genome of the electric eel (Electrophorus electricus) and sequencing electric organ and skeletal muscle transcriptomes from three lineages that have independently evolved electric organs.

A highly conserved cytoplasmic cysteine residue in the α4 nicotinic acetylcholine receptor is palmitoylated and regulates protein expression.

Nicotinic acetylcholine receptor (nAChR) cell surface expression levels are modulated during nicotine dependence and multiple disorders of the nervous system, but the mechanisms underlying nAChR trafficking remain unclear. To determine the role of cysteine residues, including their palmitoylation, on neuronal α4 nAChR subunit maturation and cell surface trafficking, the cysteines in the two intracellular regions of the receptor were replaced with serines using site-directed mutagenesis. Palmitoylation is a post-translational modification that regulates membrane receptor trafficking and function.

Placebo-controlled pilot trial of mecamylamine for treatment of autism spectrum disorders.

Objective: To explore possible benefits of a nicotinic acetylcholine receptor (nAChR) agent for autistic symptoms based on postmortem observation of nAChR abnormalities (deficient α4β2 nAChRs, excess α7 nAChRs) in brains of patients with autism.

Method: Mecamylamine, because of its safety record in children with other disorders, was chosen for this first exploration. Twenty children with autism spectrum disorder age 4-12 years were randomly assigned for 14 weeks to placebo (n=8) or mecamylamine (n=12) in ascending fixed doses: 0.

Mutations of cytosolic loop residues impair assembly and maturation of alpha7 nicotinic acetylcholine receptors.

Mechanisms that regulate early events in the biogenesis of the alpha7 nicotinic acetylcholine receptor (alpha7 AChR) are not well understood. Data presented here show that single amino acid mutations in the cytoplasmic loop of the alpha7 AChR, between position 335 and 343, abolish or attenuate expression of mature pentameric alpha7 AChRs in both human embryonic kidney tsA201 (HEK) and neuronal SH-SY5Y cells. Although the number of mature alpha7 AChRs is increased significantly in the presence of the chaperone protein resistant to inhibitors of cholineesterase-3 in HEK cells, sucrose gradient sedimentation reveals that the vast majority of alpha7 subunits are aggregated or improperly assembled.

Chronic menthol attenuates the effect of nicotine on body temperature in adolescent rats.

Menthol is a commonly used additive in tobacco products. Smoking cessation may be more difficult for smokers of mentholated cigarettes, particularly adolescent smokers. Evidence indicates that menthol can influence neurotransmitter receptors and nicotine metabolism.

Nicotine-induced Ca2+-myristoyl switch of neuronal Ca2+ sensor VILIP-1 in hippocampal neurons: a possible crosstalk mechanism for nicotinic receptors.

Visinin-like protein (VILIP-1) belongs to the neuronal Ca2+ sensor family of EF-hand Ca2+-binding proteins that regulate a variety of Ca2+-dependent signal transduction processes in neurons. It is an interaction partner of alpha4beta2 nicotinic acetylcholine receptor (nAChR) and increases surface expression level and agonist sensitivity of the receptor in oocytes. Nicotine stimulation of nicotinic receptors has been reported to lead to an increase in intracellular Ca2+ concentration by Ca2+-permeable nAChRs, which in turn might lead to activation of VILIP-1, by a mechanism described as the Ca2+-myristoyl switch.

Implication of neuronal Ca2+ -sensor protein VILIP-1 in the glutamate hypothesis of schizophrenia.

Post mortem studies in the hippocampus of schizophrenia patients revealed increased expression of neuronal Ca(2+)-sensor VILIP-1 (visinin-like protein) and enhanced co-localization with alpha4beta2 nAChR in interneurons. To study the pathological role of VILIP-1, particularly in interneurons, in the context of the glutamate hypothesis of schizophrenia, we have used ketamine-treated rats, a NMDA receptor hypofunction model, and hippocampal cultures as model systems for schizophrenia. Treatment with ketamine leads to enhanced VILIP-1 expression in interneurons in rat hippocampal CA1 region.

Menthol and nicotine oppositely modulate body temperature in the rat.

Menthol is a prominent additive in many tobacco products. To investigate possible interactions with nicotine, (-)-menthol (200 or 400 mg/kg) and (-)-nicotine (0.5 mg/kg) were injected subcutaneously in rats, and body temperature, which is modulated by brain nicotinic acetylcholine receptors, was measured.

Structural determinants of alpha4beta2 nicotinic acetylcholine receptor trafficking.

The structural determinants of nicotinic acetylcholine receptor (AChR) trafficking have yet to be fully elucidated. Hydrophobic residues occur within short motifs important for endoplasmic reticulum (ER) export or endocytotic trafficking. Hence, we tested whether highly conserved hydrophobic residues, primarily leucines, in the cytoplasmic domain of the alpha4beta2 AChR subunits were required for cell surface expression of alpha4beta2 AChRs.

Neuronal Ca2+ sensor protein VILIP-1 affects cGMP signalling of guanylyl cyclase B by regulating clathrin-dependent receptor recycling in hippocampal neurons.

The family of neuronal Ca2+ sensor (NCS) proteins is known to influence a variety of physiological and pathological processes by affecting signalling of different receptors and ion channels. Recently, it has been shown that the NCS protein VILIP-1 influences the activity of the receptor guanylyl cyclase GC-B. In transfected cell lines, VILIP-1 performs a Ca2+-dependent membrane association, the reversible Ca2+-myristoyl switch of VILIP-1, which leads to an increase in natriuretic peptide-stimulated cGMP levels.

The calcium sensor protein visinin-like protein-1 modulates the surface expression and agonist sensitivity of the alpha 4beta 2 nicotinic acetylcholine receptor.

The calcium sensor protein visinin-like protein-1 (VILIP-1) was isolated from a brain cDNA yeast two-hybrid library using the large cytoplasmic domain of the alpha4 subunit as a bait. VILIP-1 is a myristoylated calcium sensor protein that contains three functional calcium binding EF-hand motifs. The alpha4 subunit residues 302-339 were found to be essential for the interaction with VILIP-1.

Functional analysis of calcium-binding EF-hand motifs of visinin-like protein-1.

Visinin-like protein-1 (VILIP-1), a myristoylated calcium sensor protein with three EF-hand motifs, modulates adenylyl cyclase activity. It translocates to membranes when a postulated "calcium-myristoyl switch" is triggered by calcium-binding to expose its sequestered myristoyl moiety. We investigated the contributions of the EF-hand motifs to the translocation of VILIP-1 to membranes and to the modulation of adenylyl cyclase activity.