Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0011570 (
depression
)
172,036
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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.
...
PMID:Truncations of amphiphysin I by calpain inhibit vesicle endocytosis during neural hyperexcitation. 1754 3
