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Xiang-Wei Kong, Dong-Hui Wang, Cheng-Jie Zhou, Hong-Xia Zhou, Cheng-Guang Liang
Kinesin family member 1B (KIF1B) is an important microtubule-dependent monomeric motor in mammals, although little is known about its role in meiosis. We profiled KIF1B expression and localization during oocyte maturation and early embryonic development in mice, revealing a dynamic pattern throughout meiotic progression. Depletion or inhibition of KIF1B leads to abnormal polar body extrusion, disordered spindle dynamics, defects in chromosome congression, increased aneuploidy, and impaired embryonic development...
October 3, 2016: Molecular Reproduction and Development
Catherine M Drerup, Sarah Lusk, Alex Nechiporuk
UNLABELLED: Delivery of proteins and organelles to the growth cone during axon extension relies on anterograde transport by kinesin motors. Though critical for neural circuit development, the mechanisms of cargo-specific anterograde transport during axon extension are only starting to be explored. Cargos of particular importance for axon outgrowth are microtubule modifiers, such as SCG10 (Stathmin-2). SCG10 is expressed solely during axon extension, localized to growth cones, and essential for axon outgrowth; however, the mechanisms of SCG10 transport and activity were still debated...
June 29, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Jun-Hu Chen, Yan-Yan Wang, Wei-Biao Lv, Yu Gan, Wei Chang, Na-Na Tian, Xiao-Hui Huang, Li Liu, Xin-Fa Yu, Si-Dong Chen
AIM: To examine the effect of the potential interaction between KIF1B variants (rs17401966 and rs3748578) and environmental factors on the risk of hepatocellular carcinoma (HCC) in a high-risk region in China. METHODS: Three hundred and six patients with HCC and 306 hospital-based control participants residing in the Shunde region of Guangdong Province, China were enrolled. Clinical characteristics were collected by reviewing the complete medical histories from the patient archives, and epidemiological data were collected using a questionnaire and clinical examination...
April 28, 2016: World Journal of Gastroenterology: WJG
Zhang'e Choo, Rachel Yu Lin Koh, Karin Wallis, Timothy Jia Wei Koh, Chik Hong Kuick, Veronica Sobrado, Rajappa S Kenchappa, Amos Hong Pheng Loh, Shui Yen Soh, Susanne Schlisio, Kenneth Tou En Chang, Zhi Xiong Chen
Neuroblastoma is an aggressive, relapse-prone childhood tumor of the sympathetic nervous system. Current treatment modalities do not fully exploit the genetic basis between the different molecular subtypes and little is known about the targets discovered in recent mutational and genetic studies. Neuroblastomas with poor prognosis are often characterized by 1p36 deletion, containing the kinesin gene KIF1B. Its beta isoform, KIF1Bβ, is required for NGF withdrawal-dependent apoptosis, mediated by the induction of XIAP-associated Factor 1 (XAF1)...
June 7, 2016: Oncotarget
Magdalena Kuźma-Kozakiewicz, Beata Kaźmierczak, Agnieszka Chudy, Beata Gajewska, Anna Barańczyk-Kuźma
BACKGROUND: Sporadic amyotrophic lateral sclerosis (SALS) is a fatal motor neuron degenerative disease of unclear pathogenesis. Disturbances of intracellular transport are possible causes of the disease. OBJECTIVE: We evaluated the expression of motor proteins involved in the anterograde (kinesins KIF1B, KIF5C) and retrograde (KIFC3, dynactin subunits DCTN1 and DCTN3) intracellular transport in peripheral blood mononuclear cells (PBMCs). MATERIALS AND METHODS: PBMCs were obtained from 74 SALS patients with different clinical phenotypes, 65 blood donors (healthy control I), and 29 cases with other neurological diseases (disease control II) divided into subgroups IIA (atypical parkinsonism) and IIB (ALS-mimicking disorders)...
2016: Neuro-degenerative Diseases
Suja Pillai, Vinod Gopalan, Robert A Smith, Alfred K-Y Lam
Genetic mutations of phaeochromocytoma (PCC) and paraganglioma (PGL) are mainly classified into two major clusters. Cluster 1 mutations are involved with the pseudo hypoxic pathway and comprised of PHD2, VHL, SDHx, IDH, HIF2A, MDH2 and FH mutated PCC/PGL. Cluster 2 mutations are associated with abnormal activation of kinase signalling pathways and included mutations of RET, NF1, KIF1Bβ, MAX and TMEM127. In addition, VHL, SDHx (cluster 1 genes) and RET, NF1 (cluster 2 genes) germline mutations are involved in the neuronal precursor cell pathway in the pathogeneses of PCC/PGL...
April 2016: Critical Reviews in Oncology/hematology
Shuijie Li, Stuart M Fell, Olga Surova, Erik Smedler, Karin Wallis, Zhi Xiong Chen, Ulf Hellman, John Inge Johnsen, Tommy Martinsson, Rajappa S Kenchappa, Per Uhlén, Per Kogner, Susanne Schlisio
KIF1Bβ is a candidate 1p36 tumor suppressor that regulates apoptosis in the developing sympathetic nervous system. We found that KIF1Bβ activates the Ca(2+)-dependent phosphatase calcineurin (CN) by stabilizing the CN-calmodulin complex, relieving enzymatic autoinhibition and enabling CN substrate recognition. CN is the key mediator of cellular responses to Ca(2+) signals and its deregulation is implicated in cancer, cardiac, neurodegenerative, and immune disease. We show that KIF1Bβ affects mitochondrial dynamics through CN-dependent dephosphorylation of Dynamin-related protein 1 (DRP1), causing mitochondrial fission and apoptosis...
January 25, 2016: Developmental Cell
Craig Blackstone
Neuroblastomas are associated with KIF1Bβ mutations within tumor suppressor region 1p36. In this issue of Developmental Cell, Li et al. (2016) show that KIF1Bβ binding releases calcineurin autoinhibition, leading to dephosphorylation of the DRP1 GTPase and subsequent mitochondrial fragmentation. KIF1Bβ impairment causes mitochondrial hyperfusion, impairing developmental apoptosis and promoting tumorigenesis.
January 25, 2016: Developmental Cell
Marcia Helena Soares Costa, Tania M Ortiga-Carvalho, Alice Dutra Violante, Mario Vaisman
Pheochromocytomas (PCCs) and paragangliomas (PGLs) are neuroendocrine tumors derived from the chromaffin tissue. Diagnosis of these tumors is extremely important as they are linked to the hypertension syndrome with great cardiovascular morbidity and mortality. A great majority of PCCs and PGLs are sporadic and benign tumors; however, the classic idea of 10% exception of these features is changing. The description of new genes linked to familial forms of PCC/PGLs, such as succinate dehydrogenase (SDH) complex subunits, KIF1Bβ, EGLN1, TMEM127, and MAX, added to the well-known PCC familial syndrome (MEN2, VHL, and neurofibromatosis type 1) presents new challenges for diagnosis...
2015: Frontiers in Endocrinology
Kentaro Matsuura, Masanori Isogawa, Yasuhito Tanaka
The clinical course of hepatitis B virus (HBV) infection greatly differs in individuals. Various viral, host, and environmental factors influence the natural history of HBV infection. Recent genome-wide association studies identified several host genetic factors influencing the clinical course of HBV infection. Genetic variations in HLA class II loci were significantly associated with susceptibility to persistent HBV infection. Other polymorphisms in or near the genes EHMT2, TCF19, and HLA-C, located near HLA class II loci, and UBE2L3 were also associated with persistent HBV infection...
March 2016: Journal of Medical Virology
Song-Zhu Yang, Jian-Tao Wang, Wei-Wei Yu, Qing Liu, Yan-Fang Wu, Shu-Guang Chen
AIM: To compare kinesin family member 1B (KIF1B) expression with clinicopathologic parameters and prognosis in hepatocellular carcinoma (HCC) patients. METHODS: KIF1B protein and mRNA expression was assessed in HCC and paracarcinomatous (PC) tissues from 68 patients with HCC using Western blot and quantitative real-time reverse transcription-PCR, respectively. Student's t-tests were used to analyze relationships between clinicopathologic parameters and KIF1B expression, the Kaplan-Meier method was used to analyze survival outcomes, and the log-rank test was used to compare survival differences between groups...
July 21, 2015: World Journal of Gastroenterology: WJG
Huanhuan Pan, Chenghao Su, Yong Lin, Jianjun Niu
OBJECTIVE: To study the relationship between SNP rs17401966 at the KIF1B gene and the genetic susceptibility to Hepatocellular carcinoma (HCC). METHODS: All study objects were recruited from two Grade A hospitals of Amoy from January 2011 to October 2014.They were surveyed in individual matching case-control study. Accepting criterias in the cases: HCC was first diagnosed based on diagnostic basis during the investigations, over 18 years old, present addresses were as same as surveyed areas in the district (county) level range, no past history of cancers; Exclusion criterias: patients with other liver diseases...
May 2015: Zhonghua Yu Fang Yi Xue za Zhi [Chinese Journal of Preventive Medicine]
Pavle Vrebalov Cindro, Veselin Vrebalov Cindro
Following the completion of the Human Genome Project, a lot of progress has been made in understanding the genetic basis of motor neuron diseases (MNDs) and neuropathies. Spinal Muscular Atrophies (SMA) are caused by mutations in the SMN1 gene localized on Chromosome 5q11. Amyotrophic Lateral Sclerosis (ALS) has been found to have at least 18 different types, many of them associated to different genetic loci (e.g. SOD1, ALS2, SETX, FUS, VAPB, ANG, TARDBP and others), but many of the forms have still not been associated with a particular gene...
March 2015: Collegium Antropologicum
Ting-Yan Shi, Zhi Jiang, Rong Jiang, Sheng Yin, Meng-Yun Wang, Ke-Da Yu, Zhi-Ming Shao, Meng-Hong Sun, Rongyu Zang, Qingyi Wei
The kinesin-like factor 1 B (KIF1B) gene plays an important role in the process of apoptosis and the transformation and progression of malignant cells. Genetic variations in KIF1B may contribute to risk of epithelial ovarian cancer (EOC). In this study of 1,324 EOC patients and 1,386 cancer-free female controls, we investigated associations between two potentially functional single nucleotide polymorphisms in KIF1B and EOC risk by the conditional logistic regression analysis. General linear regression model was used to evaluate the correlation between the number of variant alleles and KIF1B mRNA expression levels...
September 2015: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Davide Pareyson, Paola Saveri, Anna Sagnelli, Giuseppe Piscosquito
Peripheral nerves have peculiar energetic requirements because of considerable length of axons and therefore correct mitochondria functioning and distribution along nerves is fundamental. Mitochondrial dynamics refers to the continuous change in size, shape, and position of mitochondria within cells. Abnormalities of mitochondrial dynamics produced by mutations in proteins involved in mitochondrial fusion (mitofusin-2, MFN2), fission (ganglioside-induced differentiation-associated protein-1, GDAP1), and mitochondrial axonal transport usually present with a Charcot-Marie-Tooth disease (CMT) phenotype...
June 2, 2015: Neuroscience Letters
Alexander P Drew, Danqing Zhu, Aditi Kidambi, Carolyn Ly, Shelisa Tey, Megan H Brewer, Azlina Ahmad-Annuar, Garth A Nicholson, Marina L Kennerson
Inherited peripheral neuropathies (IPNs) are a group of related diseases primarily affecting the peripheral motor and sensory neurons. They include the hereditary sensory neuropathies (HSN), hereditary motor neuropathies (HMN), and Charcot-Marie-Tooth disease (CMT). Using whole-exome sequencing (WES) to achieve a genetic diagnosis is particularly suited to IPNs, where over 80 genes are involved with weak genotype-phenotype correlations beyond the most common genes. We performed WES for 110 index patients with IPN where the genetic cause was undetermined after previous screening for mutations in common genes selected by phenotype and mode of inheritance...
March 2015: Molecular Genetics & Genomic Medicine
Joanna Solich, Magdalena Kolasa, Maciej Kuśmider, Agata Faron-Górecka, Paulina Pabian, Kinga Szafran, Dariusz Żurawek, Marta Dziedzicka-Wasylewska
BACKGROUND: These studies aimed to identify the genes differentially expressed in the frontal cortex of mice treated repeatedly with either saline or desipramine (DMI). METHODS: Differences in gene expression in the mouse frontal cortex were studied using a whole-genome microarray approach. RESULTS: The analyses revealed a group of 88 transcripts (18 genes) that were differentially expressed between the mice treated with saline and those treated with DMI...
April 2015: Pharmacological Reports: PR
Marvin Bentley, Helena Decker, Julie Luisi, Gary Banker
Identifying the proteins that regulate vesicle trafficking is a fundamental problem in cell biology. In this paper, we introduce a new assay that involves the expression of an FKBP12-rapamycin-binding domain-tagged candidate vesicle-binding protein, which can be inducibly linked to dynein or kinesin. Vesicles can be labeled by any convenient method. If the candidate protein binds the labeled vesicles, addition of the linker drug results in a predictable, highly distinctive change in vesicle localization. This assay generates robust and easily interpretable results that provide direct experimental evidence of binding between a candidate protein and the vesicle population of interest...
February 2, 2015: Journal of Cell Biology
Elisa Vitiello, Jorge G Ferreira, Helder Maiato, Maria S Balda, Karl Matter
Dividing epithelial cells need to coordinate spindle positioning with shape changes to maintain cell-cell adhesion. Microtubule interactions with the cell cortex regulate mitotic spindle positioning within the plane of division. How the spindle crosstalks with the actin cytoskeleton to ensure faithful mitosis and spindle positioning is unclear. Here we demonstrate that the tumour suppressor DLC2, a negative regulator of Cdc42, and the interacting kinesin Kif1B coordinate cell junction maintenance and planar spindle positioning by regulating microtubule growth and crosstalk with the actin cytoskeleton...
2014: Nature Communications
Hoang van Tong, C Thomas Bock, Thirumalaisamy P Velavan
Hepatitis B virus (HBV) infection is a major global health problem and many studies have underlined the importance of inter individual variability and somatic mutations during the clinical course of HBV infection. In recent years, high-throughput technologies have provided new possibilities to study the genetic basis of many diseases. We reviewed all literature available on genome-wide association studies (GWASs), whole genome, exome and RNA sequencing studies as well as studies on HBV infection and the pathogenesis of related liver disease...
October 2014: Mutation Research. Reviews in Mutation Research
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