{"title":"Drugs","authors":"G. Pugh","doi":"10.4324/9780429319303-10","DOIUrl":"https://doi.org/10.4324/9780429319303-10","url":null,"abstract":"contain inhibit induced MAPK phosphorylation. Nerve Growth Factor (NGF) induces survival and differentiation of the neural-crest derived PC12 cell line. Caveolae are cholesterol-enriched, caveolin-containing, plasma membrane microdomains involved in vesicular transport and signal transduction. Here we demonstrate the presence of caveolae in PC12 cells, and their involvement in NGF signaling. Our results showed the expression of caveolin-1 by Western blot and confocal immuno-microscopy. The presence of plasma membrane caveolae, was directly shown by rapid-freeze deep-etching electron microscopy. Moreover, combined deep-etching and immunogold techniques revealed the presence of the NGF receptor Trk A in caveolae of PC12 cells. These data, together with the cofractionation of Shc, Ras, caveolin and Trk A, in the caveolae fraction, supported a role for these plasma membrane microdomains in NGF signaling. To approach this hypothesis, caveolae were disrupted by treatment of PC12 cells with cholesterol-binding drugs. Either, filipin or cyclodextrin treatment increased basal levels of MAPK-phosphorylation. In contrast, pretreatment of PC12 cells with these drugs inhibited the NGF-, but not the EGF-, induced MAPK phosphorylation, without affecting the Trk A autophosphorylation. Taken together, our results demonstrate the presence of caveolae in PC12 cells which contain the high-affinity NGF receptor Trk A, and the specific involvement of these cholesterol-enriched plasma membrane microdomains in the propagation of the NGF-induced signal.","PeriodicalId":289065,"journal":{"name":"Psychotherapy Meets Emotional Neuroscience","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"130440182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}