@ARTICLE{Zakharov20051086,
author={Zakharov, V.V. and Bogdanova, M.N. and Mosevitsky, M.I.},
title={Specific proteolysis of neuronal protein GAP-43 by calpain: Characterization, regulation, and physiological role},
journal={Biokhimiya},
year={2005},
volume={70},
number={8},
pages={1086-1098},
note={cited By 5},
url={https://www.scopus.com/inward/record.uri?eid=2-s2.0-26844562098&partnerID=40&md5=3d358d6e03fa136f7334c7f3078e8c18},
affiliation={Molecular and Radiation Biophysics Div., Petersburg Nuclear Physics Inst., Russian Acad. of Sciences, Gatchina, Leningrad Region, 188300, Russian Federation},
abstract={The mechanism of specific proteolysis of the neuronal protein GAP-43 in axonal terminals has been investigated. In synaptic terminals in vivo and in synaptosomes in vitro GAP-43 is cleaved only at the single peptide bond formed by Ser41; this is within the main effector domain of GAP-43. Proteolysis at this site involves the cysteine calcium-dependent neutral protease calpain. The following experimental evidences support this conclusion: 1) calcium-dependent proteolysis of GAP-43 in synaptosomes is insensitive to selective inhibitor of μ-calpain (PD151746), but it is completely blocked by μ- and m-calpain inhibitor PD150606; 2) GAP-43 proteolysis in the calcium ionophore A23187-treated synaptosomes is activated by millimolar concentration of calcium ions; 3) the pattern of fragmentation of purified GAP-43 by m-calpain (but not by μ-calpain) is identical to that observed in synaptic terminals in vivo. GAP-43 phosphorylated at Ser41 by protein kinase C (PKC) is resistant to the cleavage by calpain. In addition, calmodulin binding to GAP-43 decreases the rate of calpain-mediated GAP-43 proteolysis. Our results indicate that m-calpain-mediated GAP-43 proteolysis regulated by PKC and calmodulin is of physiological relevance, particularly in axonal growth cone guidance. We suggest that the function of the N-terminal fragment of GAP-43 (residues 1-40) formed during cleavage by m-calpain consists in activation of neuronal heterotrimeric GTP-binding protein Go; this results in growth cone turning in response to repulsive signals.},
author_keywords={Calmodulin;  Calpain;  Growth cone guidance;  Neuronal protein GAP-43;  Protein kinase C;  Proteolysis;  Synaptic terminals},
correspondence_address1={Zakharov, V.V.; Molecular and Radiation Biophysics Div., Petersburg Nuclear Physics Inst., Russian Acad. of Sciences, Gatchina, Leningrad Region, 188300, Russian Federation; email: v.zakharov@vz5518.spb.edu},
issn={03209725},
coden={BIOHA},
language={Russian},
abbrev_source_title={Biokhim.},
document_type={Article},
source={Scopus},
}

{"_id":"5brCLZFM6usNSzdcb","bibbaseid":"zakharov-bogdanova-mosevitsky-specificproteolysisofneuronalproteingap43bycalpaincharacterizationregulationandphysiologicalrole-2005","author_short":["Zakharov, V.","Bogdanova, M.","Mosevitsky, M."],"bibdata":{"bibtype":"article","type":"article","author":[{"propositions":[],"lastnames":["Zakharov"],"firstnames":["V.V."],"suffixes":[]},{"propositions":[],"lastnames":["Bogdanova"],"firstnames":["M.N."],"suffixes":[]},{"propositions":[],"lastnames":["Mosevitsky"],"firstnames":["M.I."],"suffixes":[]}],"title":"Specific proteolysis of neuronal protein GAP-43 by calpain: Characterization, regulation, and physiological role","journal":"Biokhimiya","year":"2005","volume":"70","number":"8","pages":"1086-1098","note":"cited By 5","url":"https://www.scopus.com/inward/record.uri?eid=2-s2.0-26844562098&partnerID=40&md5=3d358d6e03fa136f7334c7f3078e8c18","affiliation":"Molecular and Radiation Biophysics Div., Petersburg Nuclear Physics Inst., Russian Acad. of Sciences, Gatchina, Leningrad Region, 188300, Russian Federation","abstract":"The mechanism of specific proteolysis of the neuronal protein GAP-43 in axonal terminals has been investigated. In synaptic terminals in vivo and in synaptosomes in vitro GAP-43 is cleaved only at the single peptide bond formed by Ser41; this is within the main effector domain of GAP-43. Proteolysis at this site involves the cysteine calcium-dependent neutral protease calpain. The following experimental evidences support this conclusion: 1) calcium-dependent proteolysis of GAP-43 in synaptosomes is insensitive to selective inhibitor of μ-calpain (PD151746), but it is completely blocked by μ- and m-calpain inhibitor PD150606; 2) GAP-43 proteolysis in the calcium ionophore A23187-treated synaptosomes is activated by millimolar concentration of calcium ions; 3) the pattern of fragmentation of purified GAP-43 by m-calpain (but not by μ-calpain) is identical to that observed in synaptic terminals in vivo. GAP-43 phosphorylated at Ser41 by protein kinase C (PKC) is resistant to the cleavage by calpain. In addition, calmodulin binding to GAP-43 decreases the rate of calpain-mediated GAP-43 proteolysis. Our results indicate that m-calpain-mediated GAP-43 proteolysis regulated by PKC and calmodulin is of physiological relevance, particularly in axonal growth cone guidance. We suggest that the function of the N-terminal fragment of GAP-43 (residues 1-40) formed during cleavage by m-calpain consists in activation of neuronal heterotrimeric GTP-binding protein Go; this results in growth cone turning in response to repulsive signals.","author_keywords":"Calmodulin; Calpain; Growth cone guidance; Neuronal protein GAP-43; Protein kinase C; Proteolysis; Synaptic terminals","correspondence_address1":"Zakharov, V.V.; Molecular and Radiation Biophysics Div., Petersburg Nuclear Physics Inst., Russian Acad. of Sciences, Gatchina, Leningrad Region, 188300, Russian Federation; email: v.zakharov@vz5518.spb.edu","issn":"03209725","coden":"BIOHA","language":"Russian","abbrev_source_title":"Biokhim.","document_type":"Article","source":"Scopus","bibtex":"@ARTICLE{Zakharov20051086,\r\nauthor={Zakharov, V.V. and Bogdanova, M.N. and Mosevitsky, M.I.},\r\ntitle={Specific proteolysis of neuronal protein GAP-43 by calpain: Characterization, regulation, and physiological role},\r\njournal={Biokhimiya},\r\nyear={2005},\r\nvolume={70},\r\nnumber={8},\r\npages={1086-1098},\r\nnote={cited By 5},\r\nurl={https://www.scopus.com/inward/record.uri?eid=2-s2.0-26844562098&partnerID=40&md5=3d358d6e03fa136f7334c7f3078e8c18},\r\naffiliation={Molecular and Radiation Biophysics Div., Petersburg Nuclear Physics Inst., Russian Acad. of Sciences, Gatchina, Leningrad Region, 188300, Russian Federation},\r\nabstract={The mechanism of specific proteolysis of the neuronal protein GAP-43 in axonal terminals has been investigated. In synaptic terminals in vivo and in synaptosomes in vitro GAP-43 is cleaved only at the single peptide bond formed by Ser41; this is within the main effector domain of GAP-43. Proteolysis at this site involves the cysteine calcium-dependent neutral protease calpain. The following experimental evidences support this conclusion: 1) calcium-dependent proteolysis of GAP-43 in synaptosomes is insensitive to selective inhibitor of μ-calpain (PD151746), but it is completely blocked by μ- and m-calpain inhibitor PD150606; 2) GAP-43 proteolysis in the calcium ionophore A23187-treated synaptosomes is activated by millimolar concentration of calcium ions; 3) the pattern of fragmentation of purified GAP-43 by m-calpain (but not by μ-calpain) is identical to that observed in synaptic terminals in vivo. GAP-43 phosphorylated at Ser41 by protein kinase C (PKC) is resistant to the cleavage by calpain. In addition, calmodulin binding to GAP-43 decreases the rate of calpain-mediated GAP-43 proteolysis. Our results indicate that m-calpain-mediated GAP-43 proteolysis regulated by PKC and calmodulin is of physiological relevance, particularly in axonal growth cone guidance. We suggest that the function of the N-terminal fragment of GAP-43 (residues 1-40) formed during cleavage by m-calpain consists in activation of neuronal heterotrimeric GTP-binding protein Go; this results in growth cone turning in response to repulsive signals.},\r\nauthor_keywords={Calmodulin; Calpain; Growth cone guidance; Neuronal protein GAP-43; Protein kinase C; Proteolysis; Synaptic terminals},\r\ncorrespondence_address1={Zakharov, V.V.; Molecular and Radiation Biophysics Div., Petersburg Nuclear Physics Inst., Russian Acad. of Sciences, Gatchina, Leningrad Region, 188300, Russian Federation; email: v.zakharov@vz5518.spb.edu},\r\nissn={03209725},\r\ncoden={BIOHA},\r\nlanguage={Russian},\r\nabbrev_source_title={Biokhim.},\r\ndocument_type={Article},\r\nsource={Scopus},\r\n}\r\n\r\n","author_short":["Zakharov, V.","Bogdanova, M.","Mosevitsky, M."],"key":"Zakharov20051086","id":"Zakharov20051086","bibbaseid":"zakharov-bogdanova-mosevitsky-specificproteolysisofneuronalproteingap43bycalpaincharacterizationregulationandphysiologicalrole-2005","role":"author","urls":{"Paper":"https://www.scopus.com/inward/record.uri?eid=2-s2.0-26844562098&partnerID=40&md5=3d358d6e03fa136f7334c7f3078e8c18"},"metadata":{"authorlinks":{}}},"bibtype":"article","biburl":"https://bio.pnpi.nrcki.ru/wp-content/uploads/2019/12/lbp_2019_10.txt","dataSources":["6vPsRbdrk6L6BBWH9"],"keywords":[],"search_terms":["specific","proteolysis","neuronal","protein","gap","calpain","characterization","regulation","physiological","role","zakharov","bogdanova","mosevitsky"],"title":"Specific proteolysis of neuronal protein GAP-43 by calpain: Characterization, regulation, and physiological role","year":2005}