The best studied oncogenic mechanisms are inactivating defects in both alleles of tumor suppressor genes and activating mutations in oncogenes. Chromosomal gains and losses are frequent in human tumors, but for many regions, like 1p36 and 17q in neuroblastoma, no mutated tumor suppressor genes or oncogenes were identified. Amplification of N-myc in neuroblastoma is strongly correlated with loss...

The aim of this study was to understand how molecular determinants of epithelial cells influence initial infection by herpes simplex virus type 1 (HSV-1). Upon infection of the epithelial MDCKII cell line, enhanced association of virus particles with cells forming actin protrusions was observed, suggesting a putative role of actin dynamics in HSV-1 infection. Thus, the impact of the small Rho-l...

Cdc42 GTPase plays a critical role in the establishment of cell polarity in most eukaryotic organisms. Cdc42 active state, as that of other GTPases, depends on the bound nucleotide. The protein with GTP is active, and only in this state can it interact with different target effector proteins. The spatio-temporal control of Cdc42 activity is therefore necessary to generate growth polarity. In fi...

OBJECTIVES The morphogenetic events that occur during angiogenic sprouting involve several members of the Rho family of GTPases, including Cdc42. However, the precise roles of Cdc42 in angiogenic sprouting have been difficult to elucidate owing to the lack of models to study these events in vitro. Here, we aim to identify the roles of Cdc42 in branching morphogenesis in angiogenesis. METHODS ...

PURPOSE Rho GTPases such as RAS-related C3 botulinum substrate 1 (RAC1) and cell division cycle 42 homolog (S. cerevisiae; CDC42) have been linked to cellular processes including movement, development, and apoptosis. Recently, RAC1 has been shown to be a pro-apoptotic factor in the retina during light-induced photoreceptor degeneration. Here, we analyzed the role of CDC42 in the degenerating re...

Dendritic spines are the postsynaptic terminals of most excitatory synapses in the mammalian brain. Learning and memory are associated with long-lasting structural remodeling of dendritic spines through an actin-mediated process regulated by the Rho-family GTPases RhoA, Rac, and Cdc42. These GTPases undergo sustained activation after synaptic stimulation, but whereas Rho activity can spread fro...

Malignant glioblastomas are characterized by their ability to infiltrate into normal brain. We previously reported that binding of the multifunctional cytokine TNF-like weak inducer of apoptosis (TWEAK) to its receptor fibroblast growth factor-inducible 14 (Fn14) induces glioblastoma cell invasion via Rac1 activation. Here, we show that Cdc42 plays an essential role in Fn14-mediated activation ...

Cdc42 regulates the initial establishment of cytoskeletal and junctional structures, but only little is known about its role at later stages of cellular differentiation. We studied Cdc42's role in vivo in auditory supporting cells, epithelial cells with high structural complexity. Cdc42 inactivation was induced early postnatally using the Cdc42(loxP/loxP);Fgfr3-iCre-ER(T2) mice. Cdc42 depletion...

Hair cells of the organ of Corti (OC) of the cochlea exhibit distinct planar polarity, both at the tissue and cellular level. Planar polarity at tissue level is manifested as uniform orientation of the hair cell stereociliary bundles. Hair cell intrinsic polarity is defined as structural hair bundle asymmetry; positioning of the kinocilium/basal body complex at the vertex of the V-shaped bundle...

Active Cdc42 is essential for the establishment of polarized growth. This GTPase is negatively regulated by the GTPase-activating proteins (GAPs), which are important for the spatial specificity of Cdc42 function. Rga4 is the only GAP described as negative regulator of fission yeast Cdc42. We report here that Rga6 is another fission yeast Cdc42 GAP which shares some functions with Rga4. Cells l...