title: EGFR dependent subcellular communication was responsible for morphine mediated AC superactivation.
abstract: Compensatory adenylyl cyclase (AC) superactivation has been postulated to be responsible for the development of morphine tolerance and dependence, the underlying mechanism was demonstrated to comprise c-Src-dependent upregulation of AC5 within the lipid rafts. In the present study, we demonstrated that chronic morphine treatment sensitized EGFR signaling by augmenting EGFR phosphorylation and translocation into ER, which was essential for CRT-MOR tethering within the lipid rafts and AC5 superactivation. Intriguingly, synaptic clustering of CRT-MOR was dependent on EGFR phosphorylation and presumed to implicate in alignment and organization of synaptic compartments. Taken together, our data raised the possibility that an adaptive change in MOR and EGFR signal systems might establish CRT related subcellular communication, the signaling network within brain synaptic zone was proposed to implicate in morphine tolerance and dependence.
authors.affiliation: Department of Integrative Medicine and Neurobiology, National Key lab of Medical Neurobiology, Institute of Brain Research Sciences, Shanghai Medical College, Fudan University, PR China. zhaohui07054@fudan.edu.cn
authors.forename: Hui
authors.initials: H
authors.lastname: Zhao
authors.forename: Gencheng
authors.initials: G
authors.lastname: Wu
authors.forename: Xiaoding
authors.initials: X
authors.lastname: Cao
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D037282:Calreticulin / Q000378:metabolism; D045744:Cell Line, Tumor; D000242:Cyclic AMP / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D066246:ErbB Receptors / Q000378:metabolism*; D021962:Membrane Microdomains / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D009020:Morphine / Q000494:pharmacology*; D010766:Phosphorylation; D011485:Protein Binding; D017450:Receptors, Opioid, mu / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D046509:Tissue Culture Techniques
chemical_list: D037282:Calreticulin; D017450:Receptors, Opioid, mu; D009020:Morphine; D000242:Cyclic AMP; D066246:ErbB Receptors; D000262:Adenylyl Cyclases