56 research outputs found
A CD36 ectodomain mediates insect pheromone detection via a putative tunnelling mechanism.
CD36 transmembrane proteins have diverse roles in lipid uptake, cell adhesion and pathogen sensing. Despite numerous in vitro studies, how they act in native cellular contexts is poorly understood. A Drosophila CD36 homologue, sensory neuron membrane protein 1 (SNMP1), was previously shown to facilitate detection of lipid-derived pheromones by their cognate receptors in olfactory cilia. Here we investigate how SNMP1 functions in vivo. Structure-activity dissection demonstrates that SNMP1's ectodomain is essential, but intracellular and transmembrane domains dispensable, for cilia localization and pheromone-evoked responses. SNMP1 can be substituted by mammalian CD36, whose ectodomain can interact with insect pheromones. Homology modelling, using the mammalian LIMP-2 structure as template, reveals a putative tunnel in the SNMP1 ectodomain that is sufficiently large to accommodate pheromone molecules. Amino-acid substitutions predicted to block this tunnel diminish pheromone sensitivity. We propose a model in which SNMP1 funnels hydrophobic pheromones from the extracellular fluid to integral membrane receptors
Epilepsy and intellectual disability linked protein Shrm4 interaction with GABA B Rs shapes inhibitory neurotransmission
Shrm4, a protein expressed only in polarized tissues, is encoded by the KIAA1202 gene, whose mutations have been linked to epilepsy and intellectual disability. However, a physiological role for Shrm4 in the brain is yet to be established. Here, we report that Shrm4 is localized to synapses where it regulates dendritic spine morphology and interacts with the C terminus of GABA B receptors (GABA B Rs) to control their cell surface expression and intracellular trafficking via a dynein-dependent mechanism. Knockdown of Shrm4 in rat severely impairs GABA B R activity causing increased anxiety-like behaviour and susceptibility to seizures. Moreover, Shrm4 influences hippocampal excitability by modulating tonic inhibition in dentate gyrus granule cells, in a process involving crosstalk between GABA B Rs and extrasynaptic \uce-subunit-containing GABA A Rs. Our data highlights a role for Shrm4 in synaptogenesis and in maintaining GABA B R-mediated inhibition, perturbation of which may be responsible for the involvement of Shrm4 in cognitive disorders and epilepsy
A laboratory study of the effect of acetic acid vapor on atmospheric copper corrosion
A study was made of the copper corrosion rate and corrosion products originated by the action of acetic acid vapor
at 100% relative humidity. Copper plates were exposed to an acetic acid contaminated atmosphere for a period of 21 days.
Five acetic vapor concentration levels were used. The copper corrosion rate was in the range of 1 to 23 mg/din2 day. The
corrosion-product layers were characterized using electrochemical, X-ray powder diffraction, Fourier transform infrared
spectrometry, and scanning electron microscopy techniques. Thermal and calorimetric studies were also performed. Some
of the compounds identified were cuprite (Cu,O), copper acetate hydrate [Cu(CH,COO)22H,O], and copper hydroxide
acetate [Cu4(OH)(CH,COO)72H20]. This last compound was also characterized. The thickness of the patina layers was 4
to 8 nm for amorphous cuprite, 11 to 48 nm for cuprite, and 225 nm for copper acetate. The patina, in which the cementation
process of different corrosion-product layers plays an important role, is formed by the reaction of acetic vapor with
copper through porous cuprite paths.The authors express their gratitude to the CICYT of
Spain for its financial support for Project no. QU197-0666-
C02-01. E.C. expresses his gratitude to the Spanish Ministry
of Education and Culture for the scholarshipPeer reviewe
GabaB receptor constitutents revealed by tandem affinity purification from transgenic mice
GABAB receptors function as
heterodimeric G−protein−coupled receptors
for the neurotransmitter g−aminobutyric acid
(GABA). Receptor subtypes, based on
isoforms of the ligand−binding subunit
GABAB1, are thought to involve a differential
set of associated proteins. Here, we describe
two mouse lines which allow a
straightforward biochemical isolation of
GABAB receptors. The transgenic mice
express GABAB1 isoforms that contain
sequences for a two−step affinity purification,
in addition to their endogenous subunit
repertoire. Comparative analyses of purified
samples from the transgenic mice and wildtype
control animals revealed two novel
components of the GABAB1 complex. One of
the identified proteins, potassium channel T1
domain−containing 12 (KCTD12), associates
with heterodimeric GABAB receptors via the
GABAB2 subunit. In transfected hippocampal
neurons, KCTD12 augmented axonal surface
targeting of GABAB2. The mice equipped with
tags on GABAB1 facilitate validation and
identification of native binding partners of
GABAB receptors, providing an insight into
the molecular mechanisms of synaptic
modulation
The BTB domains of the potassium channel tetramerization domain proteins prevalently assume pentameric states
Potassium channel tetramerization domain-containing (KCTD) proteins are involved in fundamental physio-pathological processes. Here, we report an analysis of the oligomeric state of the Bric-à-brack, Tram-track, Broad complex (BTB) domains of seven distinct KCTDs belonging to five major clades of the family evolution tree. Despite their functional and sequence variability, present electron microscopy data highlight the occurrence of well-defined pentameric states for all domains. Our data also show that these states coexist with alternative forms which include open pentamers. Thermal denaturation analyses conducted using KCTD1 as a model suggest that, in these proteins, different domains cooperate to their overall stability. Finally, negative-stain electron micrographs of KCTD6 in complex with Cullin3 show the presence of assemblies with a five-pointed pinwheel shape
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