%0 Journal Article
%A Wirth, Alexander
%A Chen-Wacker, Chen
%A Wu, Yao-Wen
%A Gorinski, Nataliya
%A Filippov, Mikhail A
%A Pandey, Ghanshyam
%A Ponimaskin, Evgeni
%T Dual lipidation of the brain-specific Cdc42 isoform regulates its functional properties.
%J Biochemical journal
%V 456
%N 3
%@ 0264-6021
%C London
%I Portland Press67261
%M DZNE-2020-03508
%P 311-322
%D 2013
%X Cdc42 (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.
%K Animals
%K Cell Line, Tumor
%K Cerebellum: cytology
%K Cerebellum: metabolism
%K Cysteine: genetics
%K Cysteine: metabolism
%K Dendrites: genetics
%K Dendrites: metabolism
%K Hippocampus: cytology
%K Hippocampus: metabolism
%K Humans
%K Isoenzymes: genetics
%K Isoenzymes: metabolism
%K Lipoylation: physiology
%K Mice
%K Organ Specificity: physiology
%K Protein Prenylation: physiology
%K Pseudopodia: genetics
%K Pseudopodia: metabolism
%K Transcription, Genetic: physiology
%K cdc42 GTP-Binding Protein: genetics
%K cdc42 GTP-Binding Protein: metabolism
%K Cdc42 protein, mouse (NLM Chemicals)
%K Isoenzymes (NLM Chemicals)
%K cdc42 GTP-Binding Protein (NLM Chemicals)
%K Cysteine (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:24059268
%R 10.1042/BJ20130788
%U https://pub.dzne.de/record/137186