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000137186 0247_ $$2doi$$a10.1042/BJ20130788
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000137186 0247_ $$2ISSN$$a0306-3275
000137186 0247_ $$2ISSN$$a0306-3283
000137186 0247_ $$2ISSN$$a1470-8728
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000137186 037__ $$aDZNE-2020-03508
000137186 041__ $$aEnglish
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000137186 1001_ $$0P:(DE-HGF)0$$aWirth, Alexander$$b0
000137186 245__ $$aDual lipidation of the brain-specific Cdc42 isoform regulates its functional properties.
000137186 260__ $$aLondon$$bPortland Press67261$$c2013
000137186 264_1 $$2Crossref$$3online$$bPortland Press Ltd.$$c2013-11-22
000137186 264_1 $$2Crossref$$3print$$bPortland Press Ltd.$$c2013-12-15
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000137186 3367_ $$2BibTeX$$aARTICLE
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000137186 520__ $$aCdc42 (cell division cycle 42) is a member of the Rho GTPase family which regulates a variety of cellular activities by controlling actin cytoskeleton and gene expression. Cdc42 is expressed in the form of two splice variants. The canonical Cdc42 isoform is prenylated (Cdc42-prenyl), whereas the brainspecific isoform can be palmitoylated (Cdc42-palm). In the present study we have demonstrated palmitoylation of endogenous Cdc42 in rodent and human brains and identified Cys(188) and Cys(189) as acylation sites of Cdc42-palm. Moreover, we have shown that Cys(188) can also be prenylated. Analysis of acylation-deficient mutants revealed that lipidation of Cys(188) is essential for proper membrane binding of Cdc42-palm as well as for Cdc42-mediated regulation of gene transcription and induction of densely packed filopodia in neuroblastoma cells. We also found that Cdc42-prenyl is a dominant splice variant in a wide range of commonly used cell lines as well as in the cerebellum, whereas Cdc42-palm is the main Cdc42 isoform in hippocampus, where it is critically involved in the formation of dendritic filopodia and spines. Replacement of endogenous Cdc42 by its acylation-deficient mutants revealed the importance of Cdc42-palm lipidation for its morphogenic and synaptogenic effects in neurons. These findings demonstrate that dual lipidation of Cdc42-palm represents an important regulator of morphogenic signalling in hippocampal neurons.
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000137186 650_7 $$2NLM Chemicals$$aCdc42 protein, mouse
000137186 650_7 $$2NLM Chemicals$$aIsoenzymes
000137186 650_7 $$0EC 3.6.5.2$$2NLM Chemicals$$acdc42 GTP-Binding Protein
000137186 650_7 $$0K848JZ4886$$2NLM Chemicals$$aCysteine
000137186 650_2 $$2MeSH$$aAnimals
000137186 650_2 $$2MeSH$$aCell Line, Tumor
000137186 650_2 $$2MeSH$$aCerebellum: cytology
000137186 650_2 $$2MeSH$$aCerebellum: metabolism
000137186 650_2 $$2MeSH$$aCysteine: genetics
000137186 650_2 $$2MeSH$$aCysteine: metabolism
000137186 650_2 $$2MeSH$$aDendrites: genetics
000137186 650_2 $$2MeSH$$aDendrites: metabolism
000137186 650_2 $$2MeSH$$aHippocampus: cytology
000137186 650_2 $$2MeSH$$aHippocampus: metabolism
000137186 650_2 $$2MeSH$$aHumans
000137186 650_2 $$2MeSH$$aIsoenzymes: genetics
000137186 650_2 $$2MeSH$$aIsoenzymes: metabolism
000137186 650_2 $$2MeSH$$aLipoylation: physiology
000137186 650_2 $$2MeSH$$aMice
000137186 650_2 $$2MeSH$$aOrgan Specificity: physiology
000137186 650_2 $$2MeSH$$aProtein Prenylation: physiology
000137186 650_2 $$2MeSH$$aPseudopodia: genetics
000137186 650_2 $$2MeSH$$aPseudopodia: metabolism
000137186 650_2 $$2MeSH$$aTranscription, Genetic: physiology
000137186 650_2 $$2MeSH$$acdc42 GTP-Binding Protein: genetics
000137186 650_2 $$2MeSH$$acdc42 GTP-Binding Protein: metabolism
000137186 7001_ $$0P:(DE-HGF)0$$aChen-Wacker, Chen$$b1
000137186 7001_ $$0P:(DE-HGF)0$$aWu, Yao-Wen$$b2
000137186 7001_ $$0P:(DE-HGF)0$$aGorinski, Nataliya$$b3
000137186 7001_ $$0P:(DE-2719)2810721$$aFilippov, Mikhail A$$b4$$udzne
000137186 7001_ $$0P:(DE-HGF)0$$aPandey, Ghanshyam$$b5
000137186 7001_ $$0P:(DE-HGF)0$$aPonimaskin, Evgeni$$b6$$eCorresponding author
000137186 77318 $$2Crossref$$3journal-article$$a10.1042/bj20130788$$b : Portland Press Ltd., 2013-11-22$$n3$$p311-322$$tBiochemical Journal$$v456$$x0264-6021$$y2013
000137186 773__ $$0PERI:(DE-600)1473095-9$$a10.1042/BJ20130788$$gVol. 456, no. 3, p. 311 - 322$$n3$$p311-322$$q456:3<311 - 322$$tBiochemical journal$$v456$$x0264-6021$$y2013
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000137186 9141_ $$y2013
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