J Neurosci. 2014 Aug 20; 34 (34):11461-9. doi: 10.1523/JNEUROSCI.1611-14.2014.
CM HM1, Thibault M2, Pfau M1, Heller E1, Ntsu A2, Gajewski P2, Bagot R1, Colangelo C3, Abbott T3, Rudenko G4, Neve R5, Nestler EJ1, Robison AJ6.
inahaneloang
Liphetoho tse tsitsitseng tsa polelo ea "neuronal gene" li ithutile e le babuelli ba linaha tse lemaletseng. Ntho e khahlisang haholo ke sehlahisoa sa "transcript factor" ΔFosB, sehlahisoa sa mofuta oa FosB se tsitsitseng le se tsitsitseng seo polelo ea sona e bokellaneng (NAc), e leng sebaka sa moputso oa mantlha, se hlahisoang ke ho pepeseha hoo e batlang e le lithethefatsi tsohle tsa tlhekefetso mme li laola psychomotor ea tsona le litlamorao tsa eona.
Phosphorylation ho Ser (27) e tlatsetsa ho botsitso le ho bokella ha osBFosB kamora ho pepesehela lithethefatsi khafetsa, mme omosebetsi oa morao-rao o bonts'a hore protheine kinase CaMKIIcy phosphorylates ΔFosB ho Ser (27) mme e laola botsitso ba eona ho vivo.
Mona, re supa libaka tse ling tse ling tsa ΔFosB tse kentsoeng phosphorylated in vitro ke CaMKIIcy, Thr (149) le Thr (180), 'me ba bonts'a taolo ea bona ho vivo ke cocaine e sa foleng. Re bontša hore phetoho ea phosphomimetic ea Thr (149) (T149D) e eketsa haholo ts'ebetso ea ho ngola ea AP-1 ha alanine mutation e sa ame mosebetsi oa mongolo ha e bapisoa le mofuta oa hlaha (WT) ΔFosB.
E sebelisa ho vivo viral-mediated gene fetisetsa ea ΔFosB-T149D kapa ΔFosB-T149A in mouse NAc, re ikemiselitse hore oxpxpression ea ΔFosB-T149D ho NAc e lebisa tšebetsong e kholo ea karabelo ho latela lethal dose le tlase la cocaine ho feta WT ΔFosB, ntse oxpxpression ea ΔFosB-T149A ha e hlahise maikutlo a psychomotor ho cocaine e sa foleng e tlase e bonoang kamora ho tebela ho feteletseng ha WT ΔFosB mme e tebisa tlhokomeliso e bonoang taolong ea liphoofolo maemong a holimo a cocaine.
Re boetse re bonts'a hore liphetoho tsa Thr (149) ha li ame botsitso ba ΔFosB e tebelitsoeng ho panya ea NAc, re fana ka maikutlo a hore litlamorao tsa boitšoaro ba liphetoho tsena li tsamaisoa ke thepa ea bona e fetotsoeng.
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LINKOTSO:
CaMKII; bokella; koae; phosphorylation; sengoloa; δFosB
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