| Role of mu-calpain in proteolytic cleavage of brain L-glutamic acid decarboxylase. | |
| | |
MedLine Citation:
|
PMID: 18377878 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Glutamic acid decarboxylase (GAD) is the rate-limiting enzyme for gamma-aminobutyric acid (GABA) biosynthesis. Previously, we reported the presence of truncated forms of GAD in vivo and in vitro. In addition, an unidentified endogenous protease responsible for proteolytic cleavage of full-length GAD (fGAD) to its truncated form (tGAD) was also observed. In this communication, we report that mu-calpain is a good candidate for conversion of fGAD(67) to tGAD(67). This conclusion is based on the following observations: 1. purified recombinant GAD(67) is cleaved by mu-calpain at specific sites; 2. in brain synaptosomal preparation, GAD(67) is cleaved to its truncated form by an endogenous protease which is inhibited by specific calpain inhibitors; 3. in mu-calpain knockout mice, the level of tGAD in the brain is greatly reduced compared with the wild type; 4. when mu-calpain gene is silenced by siRNA, the level of tGAD is also markedly reduced compared to the control group; and 5. mu-calpain is activated by neuronal stimulation and Ca(2+)-influx. The physiological significance of calpain in regulation of GABA synthesis and GABAergic neurotransmission is also discussed. |
| | |
Authors:
|
Di Sha; Ying Jin; Heng Wu; Jianning Wei; Chun-Hua Lin; Yi-Hsuan Lee; Chandana Buddhala; Shafi Kuchay; Athar H Chishti; Jang-Yen Wu |
Related Documents
:
|
18439218 - Co-localization of excitatory and inhibitory transmitters in the brain. 21044648 - A modified rapid enzymatic microtiter plate assay for the quantification of intracellul... 1749748 - Clonidine differentially modulates the release of endogenous gaba in various rat brain ... 18372188 - Comparative studies of 177lu-edtmp and 177lu-dotmp as potential agents for palliative r... 14756528 - Cloning and expression of pyrroloquinoline quinone (pqq) genes from a phosphate-solubil... 10561598 - Neu5acalpha3gal is part of the helicobacter pylori binding epitope in polyglycosylceram... |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. Date: 2008-03-04 |
Journal Detail:
|
Title: Brain research Volume: 1207 ISSN: 0006-8993 ISO Abbreviation: Brain Res. Publication Date: 2008 May |
Date Detail:
|
Created Date: 2008-04-18 Completed Date: 2008-08-13 Revised Date: 2009-11-18 |
Medline Journal Info:
|
Nlm Unique ID: 0045503 Medline TA: Brain Res Country: Netherlands |
Other Details:
|
Languages: eng Pagination: 9-18 Citation Subset: IM |
Affiliation:
|
Department of Biomedical Sciences, Florida Atlantic University, Boca Raton, FL 33431, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Brain / drug effects, metabolism*, ultrastructure Calcium / metabolism Calpain / pharmacology, physiology* Cells, Cultured Cyclic AMP-Dependent Protein Kinases / pharmacology Enzyme-Linked Immunosorbent Assay / methods Gene Deletion Glutamate Decarboxylase / drug effects, metabolism* Mice Mice, Knockout / genetics Neurons / drug effects, physiology Protein Processing, Post-Translational RNA, Small Interfering / genetics, pharmacology Rats Rats, Sprague-Dawley Subcellular Fractions Synaptosomes / drug effects, metabolism Transfection / methods |
| Grant Support | |
ID/Acronym/Agency:
|
NS37851/NS/NINDS NIH HHS; R01 NS037851-04/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/RNA, Small Interfering; 7440-70-2/Calcium; EC 2.7.11.11/Cyclic AMP-Dependent Protein Kinases; EC 3.4.22.-/Calpain; EC 3.4.22.-/mu-calpain; EC 4.1.1.15/Glutamate Decarboxylase; EC 4.1.1.15/glutamate decarboxylase 1 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Multielectrode array recordings reveal physiological diversity of intrinsically photosensitive retin...
Next Document: Hyperpolarization-activated current (I(h)) contributes to excitability of primary sensory neurons in...