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Kibra

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https://www.readbyqxmd.com/read/27620974/apoe-and-kibra-interactions-on-brain-functional-connectivity-in-healthy-young-adults
#1
Ningnannan Zhang, Huaigui Liu, Wen Qin, Bing Liu, Tianzi Jiang, Chunshui Yu
Genetic variations of APOE and KIBRA have been associated with human memory and Alzheimer's disease. APOE and KIBRA can jointly modulate glutamate receptor to influence long-term potentiation; however, their interactions on brain functional connectivity remain unknown. Here, we investigated additive and epistatic interactions between APOE and KIBRA (rs17070145) on brain functional connectivity density (FCD) in 267 healthy young adults. A voxel-based FCD analysis was performed to identify brain regions with significant APOE-KIBRA interaction...
September 12, 2016: Cerebral Cortex
https://www.readbyqxmd.com/read/27498008/the-memory-gene-kibra-is-a-bidirectional-regulator-of-synaptic-and-structural-plasticity-in-the-adult-brain
#2
Fabrice D Heitz, Mélissa Farinelli, Safa Mohanna, Martin Kahn, Kerstin Duning, Marco C Frey, Hermann Pavenstädt, Isabelle M Mansuy
Memory 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. Here, we show that a selective overexpression of KIBRA in neurons increases hippocampal long-term potentiation (LTP) but prevents the induction of long-term depression (LTD), and impairs spatial long-term memory in adult mice...
November 2016: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/27240404/the-regulatory-role-of-kibra-and-ptpn14-in-hippo-signaling-and-beyond
#3
REVIEW
Kayla E Wilson, Nuo Yang, Ashley L Mussell, Jianmin Zhang
The Hippo signaling pathway regulates cellular proliferation and survival, thus exerting profound effects on normal cell fate and tumorigenesis. Pivotal effectors of this pathway are YAP/TAZ, transcriptional co-activators whose dysfunction contributes to the development of cancer. Complex networks of intracellular and extracellular signaling pathways that modulate YAP and TAZ activities have recently been identified. Among them, KIBRA and PTPN14 are two evolutionarily-conserved and important YAP/TAZ upstream regulators...
2016: Genes
https://www.readbyqxmd.com/read/27220053/kibra-promotes-prostate-cancer-cell-proliferation-and-motility
#4
EDITORIAL
Seth Stauffer, Xingcheng Chen, Lin Zhang, Yuanhong Chen, Jixin Dong
KIBRA is a regulator of the Hippo-yes-associated protein (YAP) pathway, which plays a critical role in tumorigenesis. In the present study, we show that KIBRA is a positive regulator in prostate cancer cell proliferation and motility. We found that KIBRA is transcriptionally upregulated in androgen-insensitive LNCaPC4-2 and LNCaP-C81 cells compared to parental androgen-sensitive LNCaP cells. Ectopic expression of KIBRA enhances cell proliferation, migration and invasion in both immortalized and cancerous prostate epithelial cells...
May 2016: FEBS Journal
https://www.readbyqxmd.com/read/27123786/a-role-for-attention-during-wilderness-navigation-comparing-effects-of-bdnf-kibra-and-chrna4
#5
Ericka Rovira, Ryan S Mackie, Nicholas Clark, Peter N Squire, Michael D Hendricks, Alysse M Pulido, Pamela M Greenwood
OBJECTIVE: To better understand what influences interindividual differences in ability to navigate in the wilderness, we hypothesized that better performance would be seen in (a) BDNF (rs6265) Val/Val homozygotes increased use of a spatial strategy, (b) KIBRA rs17070145 T/T homozygotes superior episodic memory, (c) CHRNA4 (rs1044396) T allele carriers better ability to focus visuospatial attention. METHOD: Military cadets (n = 382) genotyped for BDNF, KIBRA, and CHRNA4 SNPs used a map and compass to navigate in unmarked woods...
September 2016: Neuropsychology
https://www.readbyqxmd.com/read/27100190/bad-ac-etylated-tau
#6
Jane C Hettinger, John R Cirrito
By using a tau construct with two mimicked acetylation sites as identified in AD brains, Tracy et al. (2016) found that acetylated tau promotes synaptic dysfunction through disruption of postsynaptic KIBRA signaling pathways, actin dynamics, and AMPA receptor trafficking.
April 20, 2016: Neuron
https://www.readbyqxmd.com/read/27041503/acetylated-tau-obstructs-kibra-mediated-signaling-in-synaptic-plasticity-and-promotes-tauopathy-related-memory-loss
#7
Tara E Tracy, Peter Dongmin Sohn, S Sakura Minami, Chao Wang, Sang-Won Min, Yaqiao Li, Yungui Zhou, David Le, Iris Lo, Ravikumar Ponnusamy, Xin Cong, Birgit Schilling, Lisa M Ellerby, Richard L Huganir, Li Gan
Tau toxicity has been implicated in the emergence of synaptic dysfunction in Alzheimer's disease (AD), but the mechanism by which tau alters synapse physiology and leads to cognitive decline is unclear. Here we report abnormal acetylation of K274 and K281 on tau, identified in AD brains, promotes memory loss and disrupts synaptic plasticity by reducing postsynaptic KIdney/BRAin (KIBRA) protein, a memory-associated protein. Transgenic mice expressing human tau with lysine-to-glutamine mutations to mimic K274 and K281 acetylation (tauKQ) exhibit AD-related memory deficits and impaired hippocampal long-term potentiation (LTP)...
April 20, 2016: Neuron
https://www.readbyqxmd.com/read/27015692/mecp2-impairs-neuronal-structure-by-regulating-kibra
#8
Alison A Williams, Robin White, Ashley Siniard, Jason Corneveaux, Matt Huentelman, Carsten Duch
Using a Drosophila model of MECP2 gain-of-function, we identified memory associated KIBRA as a target of MECP2 in regulating dendritic growth. We found that expression of human MECP2 increased kibra expression in Drosophila, and targeted RNAi knockdown of kibra in identified neurons fully rescued dendritic defects as induced by MECP2 gain-of-function. Validation in mouse confirmed that Kibra is similarly regulated by Mecp2 in a mammalian system. We found that Mecp2 gain-of-function in cultured mouse cortical neurons caused dendritic impairments and increased Kibra levels...
July 2016: Neurobiology of Disease
https://www.readbyqxmd.com/read/26989177/integrin-signalling-regulates-yap-and-taz-to-control-skin-homeostasis
#9
Ahmed Elbediwy, Zoé I Vincent-Mistiaen, Bradley Spencer-Dene, Richard K Stone, Stefan Boeing, Stefanie K Wculek, Julia Cordero, Ee H Tan, Rachel Ridgway, Val G Brunton, Erik Sahai, Holger Gerhardt, Axel Behrens, Ilaria Malanchi, Owen J Sansom, Barry J Thompson
The skin is a squamous epithelium that is continuously renewed by a population of basal layer stem/progenitor cells and can heal wounds. Here, we show that the transcription regulators YAP and TAZ localise to the nucleus in the basal layer of skin and are elevated upon wound healing. Skin-specific deletion of both YAP and TAZ in adult mice slows proliferation of basal layer cells, leads to hair loss and impairs regeneration after wounding. Contact with the basal extracellular matrix and consequent integrin-Src signalling is a key determinant of the nuclear localisation of YAP/TAZ in basal layer cells and in skin tumours...
May 15, 2016: Development
https://www.readbyqxmd.com/read/26929199/phosphorylation-dependent-regulation-of-the-dna-damage-response-of-adaptor-protein-kibra-in-cancer-cells
#10
Jayadev Mavuluri, Swarnalatha Beesetti, Rohan Surabhi, Joachim Kremerskothen, Ganesh Venkatraman, Suresh K Rayala
Multifunctional adaptor proteins encompassing various protein-protein interaction domains play a central role in the DNA damage response pathway. In this report, we show that KIBRA is a physiologically interacting reversible substrate of ataxia telangiectasia mutated (ATM) kinase. We identified the site of phosphorylation in KIBRA as threonine 1006, which is embedded within the serine/threonine (S/T) Q consensus motif, by site-directed mutagenesis, and we further confirmed the same with a phospho-(S/T) Q motif-specific antibody...
May 2016: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/26768155/serum-kibra-mrna-and-protein-expression-and-cognitive-functions-in-depression
#11
Monika Talarowska, Janusz Szemraj, Małgorzata Kowalczyk, Piotr Gałecki
BACKGROUND: Genes participating in synaptic signalling or plasticity in brain regions such as the prefrontal cortex (PFC) and the hippocampus have been implicated in cognition. Recently, a new gene (KIBRA, WWC1) has been added to this group due to its impact on memory performance. Recurrent depressive disorder (rDD) is a multifactorial disease, that one of the typical features is cognitive impairment. The main objective of this study was to perform an analysis of the KIBRA gene on both mRNA and protein levels in patients suffering from rDD and to investigate the relationship between KIBRA expression and cognitive performance...
2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/26747605/human-phosphatase-cdc14a-is-recruited-to-the-cell-leading-edge-to-regulate-cell-migration-and-adhesion
#12
Nan-Peng Chen, Borhan Uddin, Renate Voit, Elmar Schiebel
Cell adhesion and migration are highly dynamic biological processes that play important roles in organ development and cancer metastasis. Their tight regulation by small GTPases and protein phosphorylation make interrogation of these key processes of great importance. We now show that the conserved dual-specificity phosphatase human cell-division cycle 14A (hCDC14A) associates with the actin cytoskeleton of human cells. To understand hCDC14A function at this location, we manipulated native loci to ablate hCDC14A phosphatase activity (hCDC14A(PD)) in untransformed hTERT-RPE1 and colorectal cancer (HCT116) cell lines and expressed the phosphatase in HeLa FRT T-Rex cells...
January 26, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/26551466/kibra-and-apkc-regulate-starvation-induced-autophagy-in-drosophila
#13
Ahrum Jin, Thomas P Neufeld, Joonho Choe
Autophagy is a bulk degradation system that functions in response to cellular stresses such as metabolic stress, endoplasmic reticulum stress, oxidative stress, and developmental processes. During autophagy, cytoplasmic components are captured in double-membrane vesicles called autophagosomes. The autophagosome fuses with the lysosome, producing a vacuole known as an autolysosome. The cellular components are degraded by lysosomal proteases and recycled. Autophagy is important for maintaining cellular homeostasis, and the process is evolutionarily conserved...
December 4, 2015: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/26415670/investigating-the-influence-of-kibra-and-clstn2-genetic-polymorphisms-on-cross-sectional-and-longitudinal-measures-of-memory-performance-and-hippocampal-volume-in-older-individuals
#14
C J Boraxbekk, David Ames, Nicole A Kochan, Teresa Lee, Anbupalam Thalamuthu, Wei Wen, Nicola J Armstrong, John B J Kwok, Peter R Schofield, Simone Reppermund, Margaret J Wright, Julian N Trollor, Henry Brodaty, Perminder Sachdev, Karen A Mather
The variability of episodic memory decline and hippocampal atrophy observed with increasing age may partly be explained by genetic factors. KIBRA (kidney and brain expressed protein) and CLSTN2 (calsyntenin 2) are two candidate genes previously linked to episodic memory performance and volume of the hippocampus, a key memory structure. However, whether polymorphisms in these two genes also influence age-related longitudinal memory decline and hippocampal atrophy is still unknown. Using data from two independent cohorts, the Sydney Memory and Ageing Study and the Older Australian Twins Study, we investigated whether the KIBRA and CLSTN2 genetic polymorphisms (rs17070145 and rs6439886) are associated with episodic memory performance and hippocampal volume in older adults (65-90 years at baseline)...
November 2015: Neuropsychologia
https://www.readbyqxmd.com/read/26156558/impact-of-kibra-polymorphism-on-memory-function-and-the-hippocampus-in-older-adults
#15
A Veronica Witte, Theresa Köbe, Lucia Kerti, Dan Rujescu, Agnes Flöel
The single nucleotide polymorphism rs17070145 within the KIBRA gene (kidney and brain expressed protein) has been associated with variations in memory functions and related brain areas. However, previous studies yielded conflicting results, which might be due to divergent sample characteristics or task-specific effects. Therefore, we aimed to determine the impact of KIBRA genotype on learning and memory formation, and volume, microstructural integrity and functional connectivity (FC) of the hippocampus and its subfields in a well-characterized cohort of healthy older adults...
February 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/25896477/erratum-to-genetic-association-between-kibra-polymorphism-and-alzheimer-s-disease-with-in-a-japanese-population
#16
Eri Kawai, Nobuto Shibata, Tomoyuki Nagata, Shunichiro Shinagawa, Kenji Tagai, Tohru Ohnuma, Hiromi Shimazaki, Aiko Toda, Koji Kasanuki, Toshiki Takayama, Ayako Suzuki, Kazuhiko Nakayama, Hisashi Yamada, Heii Arai
No abstract text is available yet for this article.
June 2015: Neuromolecular Medicine
https://www.readbyqxmd.com/read/25832504/sox2-antagonizes-the-hippo-pathway-to-maintain-stemness-in-cancer-cells
#17
Upal Basu-Roy, N Sumru Bayin, Kirk Rattanakorn, Eugenia Han, Dimitris G Placantonakis, Alka Mansukhani, Claudio Basilico
The repressive Hippo pathway has a profound tumour suppressive role in cancer by restraining the growth-promoting function of the transcriptional coactivator, YAP. We previously showed that the stem cell transcription factor Sox2 maintains cancer stem cells (CSCs) in osteosarcomas. We now report that in these tumours, Sox2 antagonizes the Hippo pathway by direct repression of two Hippo activators, Nf2 (Merlin) and WWC1 (Kibra), leading to exaggerated YAP function. Repression of Nf2, WWC1 and high YAP expression marks the CSC fraction of the tumor population, while the more differentiated fraction has high Nf2, high WWC1 and reduced YAP expression...
2015: Nature Communications
https://www.readbyqxmd.com/read/25826608/spectrin-regulates-hippo-signaling-by-modulating-cortical-actomyosin-activity
#18
Hua Deng, Wei Wang, Jianzhong Yu, Yonggang Zheng, Yun Qing, Duojia Pan
The Hippo pathway controls tissue growth through a core kinase cascade that impinges on the transcription of growth-regulatory genes. Understanding how this pathway is regulated in development remains a major challenge. Recent studies suggested that Hippo signaling can be modulated by cytoskeletal tension through a Rok-myosin II pathway. How cytoskeletal tension is regulated or its relationship to the other known upstream regulators of the Hippo pathway remains poorly defined. In this study, we identify spectrin, a contractile protein at the cytoskeleton-membrane interface, as an upstream regulator of the Hippo signaling pathway...
2015: ELife
https://www.readbyqxmd.com/read/25814387/suppressor-of-deltex-mediates-pez-degradation-and-modulates-drosophila-midgut-homeostasis
#19
Chao Wang, Wenxiang Zhang, Meng-Xin Yin, Lianxin Hu, Peixue Li, Jiajun Xu, Hongling Huang, Shimin Wang, Yi Lu, Wenqing Wu, Margaret S Ho, Lin Li, Yun Zhao, Lei Zhang
Pez functions as an upstream negative regulator of Yorkie (Yki) to regulate intestinal stem cell (ISC) proliferation and is essential for the activity of the Hippo pathway specifically in the Drosophila midgut epithelium. Here we report that Suppressor of Deltex (Su(dx)) acts as a negative regulator of Pez. We show that Su(dx) targets Pez for degradation both in vitro and in vivo. Overexpression of Su(dx) induces proliferation in the fly midgut epithelium, which can be rescued by overexpressed Pez. We also demonstrate that the interaction between Su(dx) and Pez, bridged by WW domains and PY/PPxY motifs, is required for Su(dx)-mediated Pez degradation...
March 27, 2015: Nature Communications
https://www.readbyqxmd.com/read/25800888/genetic-association-between-kibra-polymorphism-and-alzheimer-s-disease-with-in-a-japanese-population
#20
COMPARATIVE STUDY
Eri Kawai, Nobuto Shibata, Tomoyuki Nagata, Shunichiro Shinagawa, Kenji Tagai, Kenji Tgai, Tohru Ohnuma, Hiromi Shimazaki, Aiko Toda, Koji Kasanuki, Toshiki Takayama, Ayako Suzuki, Kazuhiko Nakayama, Hisashi Yamada, Heii Arai
KIBRA plays an important role in synaptic plasticity in human hippocampus related to cognitive function. Functional studies suggest that KIBRA is a potential candidate gene for memory and Alzheimer's disease (AD) risk. A single nucleotide polymorphism, Rs17070145 C allele affects the onset of AD in an age-dependent manner comparing with T/T genotypes and is also associated with risk of substance abuse and relapse. The aim of this case-control study was to investigate whether the rs17070145 polymorphism affected the onset of AD in an age-dependent manner in a Japanese population...
June 2015: Neuromolecular Medicine
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