Unlabelled: The Hippo pathway regulates cell differentiation, proliferation, and apoptosis. Upon activation, it inhibits the import of the transcriptional coactivator yes-associated protein (YAP) into the nucleus, thus suppressing transcription of pro-proliferative genes. Hence, dynamic and precise control of the Hippo pathway is crucial for organ size control and the prevention of tumor formation.
View Article and Find Full Text PDFMemory formation is associated with activity-dependent changes in synaptic plasticity. The mechanisms underlying these processes are complex and involve multiple components. Recent work has implicated the protein KIBRA in human memory, but its molecular functions in memory processes remain not fully understood.
View Article and Find Full Text PDFSpines are small protrusions arising from dendrites that receive most excitatory synaptic input in the brain. Dendritic spines represent dynamic structures that undergo activity-dependent adaptations, for example, during synaptic plasticity. Alterations of spine morphology, changes of spine type ratios or density have consequently been found in paradigms of learning and memory, and accompany many neuropsychiatric disorders.
View Article and Find Full Text PDFThe WWC1 gene has been genetically associated with human episodic memory performance, and its product KIdney/BRAin protein (KIBRA) has been shown to interact with the atypical protein kinase protein kinase M ζ (PKMζ). Although recently challenged, PKMζ remains a candidate postsynaptic regulator of memory maintenance. Here, we show that PKMζ is subject to rapid proteasomal degradation and that KIBRA is both necessary and sufficient to counteract this process, thus stabilizing the kinase and maintaining its function for a prolonged time.
View Article and Find Full Text PDFUnlabelled: KIBRA has been described as a key regulator of the Hippo signaling pathway, regulating organ size control, cell contact inhibition, cell growth, as well as tumorigenesis and cystogenesis. Since there is scarce information on KIBRA gene expression regulation, we analyzed the molecular basis of tissue-specific KIBRA expression in human kidney epithelial (IHKE, HPCT) and neuroblastoma (SH-SY5Y, SK-SN-SH) cells. We detected four novel and differentially used transcription start sites, two of which positioned in the first intron, generating two novel alternative exons.
View Article and Find Full Text PDFKIBRA has recently been identified as a gene associated with human memory performance. Despite the elucidation of the role of KIBRA in several diverse processes in nonneuronal cells, the molecular function of KIBRA in neurons is unknown. We found that KIBRA directly binds to the protein interacting with C-kinase 1 (PICK1) and forms a complex with α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptors (AMPARs), the major excitatory neurotransmitter receptors in the brain.
View Article and Find Full Text PDFAutosomal dominant polycystic kidney disease (ADPKD) is the most frequent monogenic cause of kidney failure, characterized by the development of renal cysts. ADPKD is caused by mutations of the polycystin-1 (PC1) or polycystin-2 (PC2) genes. PC2 encodes a Ca(2+)-permeable cation channel, and its dysfunction has been implicated in cyst development.
View Article and Find Full Text PDFThe genetic locus encoding KIBRA, a member of the WWC family of proteins, has recently been shown to be associated with human memory performance through genome-wide single nucleotide polymorphism screening. Gene expression analysis and a variety of functional studies have further indicated that such a role is biologically plausible for KIBRA. Here, we review the existing literature, illustrate connections between the different lines of evidence, and derive models based on KIBRA's function(s) in the brain that can be further tested experimentally.
View Article and Find Full Text PDFThe CXC chemokine receptor 3 (CXCR3) has been linked to autoimmune and inflammatory disease, allograft rejection, and ischemic nephropathy. CXCR3 is expressed on endothelial and smooth muscle cells. Although a recent study posited that antagonizing of CXCR3 function may reduce atherosclerosis, the role of CXCR3 in controlling physiological vascular functions remains unclear.
View Article and Find Full Text PDFAsymmetric delivery and distribution of macromolecules are essential for cell polarity and for cellular functions such as differentiation, division, and signaling. Injury of podocytes, which are polarized epithelial cells, changes the dynamics of the actin meshwork, resulting in foot process retraction and proteinuria. Although the spatiotemporal control of specific protein-protein interactions is crucial for the establishment of cell polarity, the mechanisms controlling polarity-dependent differentiation and division are incompletely understood.
View Article and Find Full Text PDFDendritic transport of (m)RNA molecules and localized translation at post-synaptic sites is connected to synaptic plasticity and memory formation. Brain cytoplasmic RNA, 200nt (BC200 RNA) is a brain-specific, small non-messenger RNA with a somatodendritic distribution in primate neurons. The transcript is a component of a ribonucleoprotein particle that is thought to act as a regulator of decentralized translation in dendrites.
View Article and Find Full Text PDFKIAA0513 was previously identified as upregulated in the dorsolateral prefrontal cortex of subjects with schizophrenia by microarray analysis. In the present study, the differential expression in the schizophrenic subjects was confirmed by quantitative RT-PCR. The limited homology to proteins of known function and lack of functional domains in the encoded protein have made it difficult to predict a function for KIAA0513.
View Article and Find Full Text PDFVasopressin (VP) mRNA and the non-coding BC200 RNA are sorted to neuronal dendrites. Among proteins interacting specifically with both RNAs is the multifunctional poly(A)-binding protein (PABP) consisting of four RNA recognition motifs (RRMs) and a C-terminal auxiliary domain. The protein/RNA interaction studies presented here reveal that PABPs association with VP- and BC200 RNA is exclusively mediated by RRMs 3+4.
View Article and Find Full Text PDFBC1 RNA and BC200 RNA are two non-homologous, small non-messenger RNAs (snmRNAs) that were generated, evolutionarily, quite recently by retroposition. This process endowed the RNA polymerase III transcripts with central adenosine-rich regions. Both RNAs are expressed almost exclusively in neurons, where they are transported into dendritic processes as ribonucleoprotein particles (RNPs).
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