A novel approach for in vivo screening of toxins using the Drosophila Giant Fiber circuit.

Finding compounds that affect neuronal or muscular function is of great interest as potential therapeutic agents for a variety of neurological disorders. Alternative applications for these compounds include their use as molecular probes as well as insecticides. We have developed a bioassay that requires small amounts of compounds and allows for unbiased screening of biological activity in vivo.

Mast cell and monocyte recruitment by S100A12 and its hinge domain.

S100A12 is expressed at sites of acute, chronic, and allergic inflammation. S100 proteins have regions of high sequence homology, but the "hinge" region between the conserved calcium binding domains is structurally and functionally divergent. Because the murine S100A8 hinge domain (mS100A8(42-55)) is a monocyte chemoattractant whereas the human sequence (hS100A8(43-56)) is inactive, we postulated that common hydrophobic amino acids within the S100A12 hinge sequence may be functional.

Crystallization and preliminary X-ray diffraction of the Munc18c-syntaxin4 (1-29) complex.

The production of diffraction-quality crystals of Munc18c, a protein involved in regulating vesicular exocytosis in mammals, is reported. The diffraction resolution of Munc18c crystals was optimized by (i) cocrystallizing with a peptide fragment of the Munc18c functional binding partner syntaxin4, (ii) using nanolitre free-interface diffusion crystallization-screening chips and microlitre hanging-drop vapour diffusion and (iii) applying a post-crystallization dehydration treatment. Crystals belonging to the cubic space group P2(1)3, with unit-cell parameters a = b = c = 170.

S100A12 provokes mast cell activation: a potential amplification pathway in asthma and innate immunity.

Background: The calcium-binding protein S100A12 might provoke inflammation and monocyte recruitment through the receptor for advanced glycation end products.

Objective: Because inflammation elicited by S100A12 in vivo had characteristics of mast cell (MC) activation, we aimed to define the mechanism.

Methods: Various MC populations were used to test S100A12 activation assessed on the basis of morphology, histamine release, leukotriene production, and cytokine induction.

Molecular dissection of the Munc18c/syntaxin4 interaction: implications for regulation of membrane trafficking.

Sec1p/Munc18 (SM) proteins are believed to play an integral role in vesicle transport through their interaction with SNAREs. Different SM proteins have been shown to interact with SNAREs via different mechanisms, leading to the conclusion that their function has diverged. To further explore this notion, in this study, we have examined the molecular interactions between Munc18c and its cognate SNAREs as these molecules are ubiquitously expressed in mammals and likely regulate a universal plasma membrane trafficking step.