Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Amphiphysins, members of the BAR (Bin-Amphiphysin-Rvsp) protein super family, have been postulated to play a key role in clathrin-mediated endocytosis of synaptic vesicles (SVs). This review focuses on recent genetic studies of the role of amphiphysins in SV recycling and membrane morphogenesis. In the mouse, brain-specific amphiphysin I and II regulate, but are not essential for, SV recycling. The role of this regulation appears important, as mice deficient in these proteins have seizures and are deficient in learning and memory. In the fruit fly Drosophila melanogaster, amphiphysin is found in muscles and is enriched at postsynaptic membranes of neuromuscular junctions (NMJs); however, it does not play a role in SV recycling. Rather, amphiphysin in fly muscles appears to regulate the organization and structure of the muscle T-tubule system and possibly the subsynaptic reticulum. Amphiphysin is also involved in membrane organization in both neurons and non-neuronal cells in Drosophila. These studies reveal pleiotropic functions for amphiphysins in clathrin-mediated endocytosis and the regulation of membrane dynamics, perhaps through the actin cytoskeleton.
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PMID:Amphiphysins: raising the BAR for synaptic vesicle recycling and membrane dynamics. Bin-Amphiphysin-Rvsp. 1204 53

Under normal physiological conditions, synaptic vesicle endocytosis is regulated by phosphorylation and Ca(2+)-dependent dephosphorylation of endocytic proteins such as amphiphysin and dynamin. To investigate the regulatory mechanisms that may occur under the conditions of excessive presynaptic Ca(2+) influx observed preceding neural hyperexcitation, we examined hippocampal slices following high-potassium or high-frequency electrical stimulation (HFS). In both cases, three truncated forms of amphiphysin I resulted from cleavage by the protease calpain. In vitro, the binding of truncated amphiphysin I to dynamin I and copolymerization into rings with dynamin I were inhibited, but its interaction with liposomes was not affected. Moreover, overexpression of the truncated form of amphiphysin I inhibited endocytosis of transferrin and synaptic vesicles. Inhibiting calpain prevented HFS-induced depression of presynaptic transmission. Finally, calpain-dependent amphiphysin I cleavage attenuated kainate-induced seizures. These results suggest that calpain-dependent cleavage of amphiphysin I inhibits synaptic vesicle endocytosis during neural hyperexcitation and demonstrate a novel post-translational regulation of endocytosis.
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PMID:Truncations of amphiphysin I by calpain inhibit vesicle endocytosis during neural hyperexcitation. 1754 3

A method to evaluate kinase inhibitor action was reported [L. Morgan, S.J. Neame, H. Child, R. Chung, B. Shah, L. Barden, J.M. Staddon, T.R. Patel, Development of a pentylenetetrazole-induced seizure model to evaluate kinase inhibitor efficacy in the central nervous system, Neurosci. Lett. 395 (2006) 143-148]. In this, acute administration of the GABA antagonist pentylenetetrazole triggers seizures through glutamate-dependent pathways. Under such conditions, activation of the c-Jun N-terminal kinase (JNK) pathway was detected in hippocampal extracts. Phosphorylation of the upstream JNK kinase MKK4 was also revealed through use of a phospho-MKK4-specific antibody. Here, this antibody is shown to also react with a protein of approximately 125 kDa which underwent increased phosphorylation in response to pentylenetetrazole treatment. The present study aimed to identify the approximately 125 kDa protein as it may provide novel insight into signalling, neuronal activity and seizures. Using chromatographic methods and mass spectrometry, the protein was identified as amphiphysin I. This was confirmed by 2D gel analysis and immunoblot with amphiphysin I-specific antibodies. Although the phospho-MKK4 antibody was raised against an MKK4-specific peptide, partial sequence homology between this sequence and a region of amphiphysin was discerned. New antibodies raised against the phospho-threonine 260-amphiphysin-specific sequence detected increased phosphorylation in response to pentylenetetrazole treatment. This particular phosphorylation site does not seem to have been described before, possibly reflecting a novel regulatory aspect of amphiphysin biology. As amphiphysin is involved in the regulation of endocytosis, phosphorylation at this site may play a role in the regulated re-uptake of synaptic vesicles after neurotransmitter release.
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PMID:Amphiphysin I phosphorylation on residue threonine 260 in a pentylenetetrazole-induced seizure model. 1876 Oct 55