136 research outputs found
Ba2+ replaces Ca2+/calmodulin in the activation of protein phosphates and in exocytosis of all major transmitters
Identification of Srp9 as a febrile seizure susceptibility gene
Objective: Febrile seizures (FS) are the most common seizure type in young children. Complex FS are a risk factor for mesial temporal lobe epilepsy (mTLE). To identify new FS susceptibility genes we used a forward genetic strategy in mice and subsequently analyzed candidate genes in humans. Methods: We mapped a quantitative trait locus (QTL1) for hyperthermia-induced FS on mouse chromosome 1, containing the signal recognition particle 9 (Srp9) gene. Effects of differential Srp9 expression were assessed in vivo and in vitro. Hippocampal SRP9 expression and genetic association were analyzed in FS and mTLE patients. Results: Srp9 was differentially expressed between parental strains C57BL/6J and A/J. Chromosome substitution strain 1 (CSS1) mice exhibited lower FS susceptibility and Srp9 expression than C57BL/6J mice. In vivo knockdown of brain Srp9 reduced FS susceptibility. Mice with reduced Srp9 expression and FS susceptibility, exhibited reduced hippocampal AMPA and NMDA currents. Downregulation of neuronal Srp9 reduced surface expression of AMPA receptor subunit GluA1. mTLE patients with antecedent FS had higher SRP9 expression than patients without. SRP9 promoter SNP rs12403575(G/A) was genetically associated with FS and mTLE. Interpretation: Our findings identify SRP9 as a novel FS susceptibility gene and indicate that SRP9 conveys its effects through endoplasmic reticulum (ER)-dependent synthesis and trafficking of membrane proteins, such as glutamate receptors. Discovery of this new FS gene and mechanism may provide new leads for early diagnosis and treatment of children with complex FS at risk for mTLE
The role of neuron-specific kinase C substrate protein B-50 in receptor-mediated polyphosphoinositide hydrolysis
Irreversible stimulation of Xenopus melanophores by photoaffinity labelling with p-azidophenylalanine13-α-melanotropin
α-melanotropin induces pigment dispersion in
melanophores and pigment formation in melanocytes
and melanoma cells. The pigmentdispersingeffect
of MSH is completely reversible in vitro, as the
melanosomes reaggregate readily upon removal of
the hormone. The primary site of action of α-MSH
appears to be a cell surface receptor, which can be
stimulated by two different portions of the α-MSH
molecule, namely the central (-Glu-His-Phe-Arg-
Trp-) and the C-terminal (-Gly-Lys-Pro-Val .
NHâ‚‚) message sequences. The C-terminal residue
is essential for the interaction with the receptor, since
its absence reduces the biological activity considerably
(in preparation); the structure of its side-chain, however,
is less important, and it may therefore contain
an affinity label
Presynaptic PKC substrate B-50 (GAP-43) and neurotransmitter release : studies with permeated synaptosomes
Development of a single cell Ca2+ imaging system to study the role of PKC substrate B 50 in neurotransmitter release and neurite outgrowth
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