Structural domains involved in the regulation of transmitter release by synapsins

Author Posting. © Society for Neuroscience, 2005. This article is posted here by permission of Society for Neuroscience for personal use, not for redistribution. The definitive version was published in Journal of Neuroscience 25 (2005): 2658-2669, doi:10.1523/JNEUROSCI.4278-04.2005.Synapsins are a family of neuron-specific phosphoproteins that regulate neurotransmitter release by associating with synaptic vesicles. Synapsins consist of a series of conserved and variable structural domains of unknown function. We performed a systematic structure-function analysis of the various domains of synapsin by assessing the actions of synapsin fragments on neurotransmitter release, presynaptic ultrastructure, and the biochemical interactions of synapsin. Injecting a peptide derived from domain A into the squid giant presynaptic terminal inhibited neurotransmitter release in a phosphorylation-dependent manner. This peptide had no effect on vesicle pool size, synaptic depression, or transmitter release kinetics. In contrast, a peptide fragment from domain C reduced the number of synaptic vesicles in the periphery of the active zone and increased the rate and extent of synaptic depression. This peptide also slowed the kinetics of neurotransmitter release without affecting the number of docked vesicles. The domain C peptide, as well as another peptide from domain E that is known to have identical effects on vesicle pool size and release kinetics, both specifically interfered with the binding of synapsins to actin but not with the binding of synapsins to synaptic vesicles. This suggests that both peptides interfere with release by preventing interactions of synapsins with actin. Thus, interactions of domains C and E with the actin cytoskeleton may allow synapsins to perform two roles in regulating release, whereas domain A has an actin-independent function that regulates transmitter release in a phosphorylation-sensitive manner.This work was supported by grants from The Fisher Center for Alzheimer’s Disease Research (P.G., F.B.), National Institutes of Health Grants NS-21624 (G.J.A.) and MH39327 (P.G.), the Italian Ministry of Education (F.B.), Consorzio Italiano Biotecnologie (F.B.), and a Ramon y Cajal fellowship (S.H.)

Entropy stable numerical approximations for the isothermal and polytropic Euler equations

In this work we analyze the entropic properties of the Euler equations when the system is closed with the assumption of a polytropic gas. In this case, the pressure solely depends upon the density of the fluid and the energy equation is not necessary anymore as the mass conservation and momentum conservation then form a closed system. Further, the total energy acts as a convex mathematical entropy function for the polytropic Euler equations. The polytropic equation of state gives the pressure as a scaled power law of the density in terms of the adiabatic index γ. As such, there are important limiting cases contained within the polytropic model like the isothermal Euler equations (γ = 1) and the shallow water equations (γ = 2). We first mimic the continuous entropy analysis on the discrete level in a finite volume context to get special numerical flux functions. Next, these numerical fluxes are incorporated into a particular discontinuous Galerkin (DG) spectral element framework where derivatives are approximated with summation-by-parts operators. This guarantees a high-order accurate DG numerical approximation to the polytropic Euler equations that is also consistent to its auxiliary total energy behavior. Numerical examples are provided to verify the theoretical derivations, i.e., the entropic properties of the high order DG scheme

Identification and thermochemical analysis of high-lignin feedstocks for biofuel and biochemical production

Background - Lignin is a highly abundant biopolymer synthesized by plants as a complex component of plant secondary cell walls. Efforts to utilize lignin-based bioproducts are needed. Results - Herein we identify and characterize the composition and pyrolytic deconstruction characteristics of high-lignin feedstocks. Feedstocks displaying the highest levels of lignin were identified as drupe endocarp biomass arising as agricultural waste from horticultural crops. By performing pyrolysis coupled to gas chromatography-mass spectrometry, we characterized lignin-derived deconstruction products from endocarp biomass and compared these with switchgrass. By comparing individual pyrolytic products, we document higher amounts of acetic acid, 1-hydroxy-2-propanone, acetone and furfural in switchgrass compared to endocarp tissue, which is consistent with high holocellulose relative to lignin. By contrast, greater yields of lignin-based pyrolytic products such as phenol, 2-methoxyphenol, 2-methylphenol, 2-methoxy-4-methylphenol and 4-ethyl-2-methoxyphenol arising from drupe endocarp tissue are documented. Conclusions - Differences in product yield, thermal decomposition rates and molecular species distribution among the feedstocks illustrate the potential of high-lignin endocarp feedstocks to generate valuable chemicals by thermochemical deconstruction

Tonically active protein kinase A regulates neurotransmitter release at the squid giant synapse

Electrophysiological and microinjection methods were used to examine the role of cyclic AMP-dependent protein kinase A (PKA) in regulating transmitter release at the squid giant synapse.Excitatory postsynaptic potentials (EPSPs) evoked by presynaptic action potentials were not affected by presynaptic injection of an exogenous active catalytic subunit of mammalian PKA.In contrast, presynaptic injection of PKI-amide, a peptide that inhibits PKA with high potency and specificity, led to a reversible inhibition of EPSPs.Injection of several other peptides that serve as substrates for PKA also reversibly inhibited neurotransmitter release. The ability of these peptides to inhibit release was correlated with their ability to serve as PKA substrates, suggesting that these peptides act by competing with endogenous substrates for phosphorylation by active endogenous PKA.We suggest that the phosphorylation of PKA substrates is maintained at a relatively high state under basal conditions and that this tonic activity of PKA is to a large degree required for evoked neurotransmitter release at the squid giant presynaptic terminal

Entropy stable numerical approximations for the isothermal and polytropic Euler equations

In this work we analyze the entropic properties of the Euler equations when the system is closed with the assumption of a polytropic gas. In this case, the pressure solely depends upon the density of the fluid and the energy equation is not necessary anymore as the mass conservation and momentum conservation then form a closed system. Further, the total energy acts as a convex mathematical entropy function for the polytropic Euler equations. The polytropic equation of state gives the pressure as a scaled power law of the density in terms of the adiabatic index gamma As such, there are important limiting cases contained within the polytropic model like the isothermal Euler equations (gamma=1 and the shallow water equations (gamma=2 We first mimic the continuous entropy analysis on the discrete level in a finite volume context to get special numerical flux functions. Next, these numerical fluxes are incorporated into a particular discontinuous Galerkin (DG) spectral element framework where derivatives are approximated with summation-by-parts operators. This guarantees a high-order accurate DG numerical approximation to the polytropic Euler equations that is also consistent to its auxiliary total energy behavior. Numerical examples are provided to verify the theoretical derivations, i.e., the entropic properties of the high order DG scheme