Journal Article

DZNE-2020-03508

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Dual lipidation of the brain-specific Cdc42 isoform regulates its functional properties.

Wirth, A. ; Chen-Wacker, C. ; Wu, Y.-W. ; Gorinski, N. ; Filippov, M. A.DZNE* ; Pandey, G. ; Ponimaskin, E. (Corresponding author)

2013
Portland Press67261 London

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Please use a persistent id in citations: doi:10.1042/BJ20130788

Abstract: 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.

Keyword(s): Animals (MeSH) ; Cell Line, Tumor (MeSH) ; Cerebellum: cytology (MeSH) ; Cerebellum: metabolism (MeSH) ; Cysteine: genetics (MeSH) ; Cysteine: metabolism (MeSH) ; Dendrites: genetics (MeSH) ; Dendrites: metabolism (MeSH) ; Hippocampus: cytology (MeSH) ; Hippocampus: metabolism (MeSH) ; Humans (MeSH) ; Isoenzymes: genetics (MeSH) ; Isoenzymes: metabolism (MeSH) ; Lipoylation: physiology (MeSH) ; Mice (MeSH) ; Organ Specificity: physiology (MeSH) ; Protein Prenylation: physiology (MeSH) ; Pseudopodia: genetics (MeSH) ; Pseudopodia: metabolism (MeSH) ; Transcription, Genetic: physiology (MeSH) ; cdc42 GTP-Binding Protein: genetics (MeSH) ; cdc42 GTP-Binding Protein: metabolism (MeSH) ; Cdc42 protein, mouse ; Isoenzymes ; cdc42 GTP-Binding Protein ; Cysteine

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Contributing Institute(s):

1. Molecular Neuroplasticity (AG Dityatev)

Research Program(s):

1. 342 - Disease Mechanisms and Model Systems (POF3-342) (POF3-342)

Appears in the scientific report 2013

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Database coverage:
; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF < 5 ; JCR ; NCBI Molecular Biology Database ; PubMed Central ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection

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