Dual lipidation of the brain-specific Cdc42 isoform regulates its functional properties.
نویسندگان
چکیده
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.
منابع مشابه
P-121: Cloning and Expression of The Inosine Triphosphate Pyrophosphatase Gene Variant II in E.coli
Background Environmental and cellular inappropriate conditions can cause damages to cells nucleotide poll. Deamination and oxidation damages interfere with cell�s vital reactions. Inosine triphosphate pyrophosphatase (ITPA), an evolutionary conserved enzyme, plays a critical role in elimination of non-canonical bases. In human genome, the ITPA gene is located on chromosome 20 short arm and tran...
متن کاملmicroRNA-33 Regulates ApoE Lipidation and Amyloid-β Metabolism in the Brain.
UNLABELLED Dysregulation of amyloid-β (Aβ) metabolism is critical for Alzheimer's disease (AD) pathogenesis. Mounting evidence suggests that apolipoprotein E (ApoE) is involved in Aβ metabolism. ATP-binding cassette transporter A1 (ABCA1) is a key regulator of ApoE lipidation, which affects Aβ levels. Therefore, identifying regulatory mechanisms of ABCA1 expression in the brain may provide new ...
متن کاملRhoGEF9 splice isoforms influence neuronal maturation and synapse formation downstream of α2 GABAA receptors
In developing brain neuronal migration, dendrite outgrowth and dendritic spine outgrowth are controlled by Cdc42, a small GTPase of the Rho family, and its activators. Cdc42 function in promoting actin polymerization is crucial for glutamatergic synapse regulation. Here, we focus on GABAergic synapse-specific activator of Cdc42, collybistin (CB) and examine functional differences between its sp...
متن کاملTHE MORPHO-FUNCTIONAL STATE OF THE BRAIN UNDER CONDITIONS OF HYPOKINESIA AND ITS POSSIBLE PHARMACOLOGICAL CORRECTION BY GABA-ERGIC SUBSTANCES
In this paper it has been shown that deterioration of the brain cortex capillary system and negative dynamics of cerebral tissue morphology occur under conditions of hypo kinesia. Simultaneously, gamma-aminobutyric acid (GABA) and piracetam have been shown to favor the development of vasodilation and prevent further worsening of the cerebral blood supply. During the experiment, it was also ...
متن کاملKCC2 regulates actin dynamics in dendritic spines via interaction with β-PIX
Chloride extrusion in mature neurons is largely mediated by the neuron-specific potassium-chloride cotransporter KCC2. In addition, independently of its chloride transport function, KCC2 regulates the development and morphology of dendritic spines through structural interactions with the actin cytoskeleton. The mechanism of this effect remains largely unknown. In this paper, we show a novel pat...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- The Biochemical journal
دوره 456 3 شماره
صفحات -
تاریخ انتشار 2013