The Arabidopsis FRA1 kinesin contributes to the organization of cellulose microfibrils through an unknown mechanism. The cortical localization of this kinesin during interphase raises the possibility that it transport...The Arabidopsis FRA1 kinesin contributes to the organization of cellulose microfibrils through an unknown mechanism. The cortical localization of this kinesin during interphase raises the possibility that it transports cell wallrelated cargoes along cortical microtubules that either directly or indirectly influence cellulose microfibril patterning. To determine whether FRA1 is an authentic motor protein, we combined bulk biochemical assays and single molecule fluorescence imaging to analyze the motor properties of recombinant, GFP-tagged FRA1 containing the motor and coiled-coil domains （designated as FRAI（707）-GFP）. We found that FRAI（707）-GFP binds to microtubules in an ATP-dependent manner and that its ATPase activity is dramatically stimulated by the presence of microtubules. Using single molecule studies, we found that FRAI（707）-GFP moves processively along microtubule tracks at a velocity of about 0.4 μm s-1. In addition, we found that FRAI（707）-GFP is a microtubule plus-end-directed motor and that it moves along microtubules as a dimer. Interestingly, our single molecule analysis shows that the processivity of FRAI（707）-GFP is at least twice the processivity of conventional kinesin, making FRA1 the most processive kinesin to date. Together, our data show that FRA1 is a bona fide motor protein that has the potential to drive Iong-distance transport of cargo along cortical microtubules.展开更多
Entosis, a ceU-in-ceU process, has been implicated in the formation of aneuploidy associated with an aberrant cell division control. Microtubule plus-end-tracking protein TI P150 facilitates the loading of MCAK onto t...Entosis, a ceU-in-ceU process, has been implicated in the formation of aneuploidy associated with an aberrant cell division control. Microtubule plus-end-tracking protein TI P150 facilitates the loading of MCAK onto the microtubule plus ends and orchestrates micro- tubule plus-end dynamics during cell division. Here we show that TIP150 cooperates with MCAK to govern entosis via a regulatory cir- cuitry that involves Aurora A-mediated phosphorylation of MCAK. Our biochemical analyses show that MCAK forms an intra-molecular association, which is essential for TIP150 binding. Interestingly, Aurora A-mediated phosphorylation of MCAK modulates its intra-mo- lecular association, which perturbs the MCAK-TI P150 interaction in vitro and inhibits entosis in vivo. To probe if MCAK-TIP150 inter- action regulates microtubule plasticity to affect the mechanical properties of ceUs during entosis, we used an optical trap to measure the mechanical rigidity of live MCF7 ceils. We find that the MCAK cooperates with TIP150 to promote microtubule dynamics and modulate the mechanical rigidity of the cells during entosis. Our results show that a dynamic interaction of MCAK-TI P150 orchestrated by Aurora A-mediated phosphorylation governs entosis via regulating microtubule plus-end dynamics and cell rigidity. These data reveal a previously unknown mechanism of Aurora A regulation in the control of microtubule plasticity during ceU-in-ceU pro- cesses.展开更多
AIM: To examine the effect of the potential interaction between KIF1 B variants(rs17401966 and rs3748578) and environmental factors on the risk of hepatocellular carcinoma(HCC) in a high-risk region in China.METHODS: ...AIM: To examine the effect of the potential interaction between KIF1 B 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. Two single nucleotide polymorphisms(SNPs) of KIF1B(rs17401966 and rs3748578) were chosen for the current study. All subjects were genotypedusing a Taq Man real-time polymerase chain reaction. Multiplicative and additive logistic regression models were used to evaluate various gene-environment interactions.RESULTS: Smoking, frequent consumption of raw freshwater fish, hepatitis B virus(HBV) infection, and a family history of HCC were important risk factors for HCC in this population. Chronic infection with HBV was the most important environmental risk factor for HCC [odds ratio(OR) = 12.02; 95% confidence interval(95%CI): 6.02-24.00]. No significant association was found between the KIF1 B variants alone and the risk of HCC. Nevertheless, a significant additive effect modification was observed between rs17401966 and alcohol consumption(P for additive interaction = 0.0382). Compared with non-drinkers carrying either the AG or GG genotype of rs17401966, individuals classified as alcohol consumers with the AA genotype of rs17401966 had a significantly increased risk of HCC(OR = 2.36; 95%CI: 1.49-3.74).CONCLUSION: The gene-environment interaction between the KIF1 B rs17401966 variant and alcohol consumption may contribute to the development of HCC in Chinese individuals.展开更多
Male sterility is an essential trait in hybrid seed production,especially for monoclinous and autogamous food crops.Soybean male-sterile ms1 mutant has been known for more than 50 years and could be instrumental in ma...Male sterility is an essential trait in hybrid seed production,especially for monoclinous and autogamous food crops.Soybean male-sterile ms1 mutant has been known for more than 50 years and could be instrumental in making hybrid seeds.However,the gene responsible for the male-sterile phenotype has remained unknown.Here,we report the map-based cloning and characterization of the MS1 gene in soybean.MS1 encodes a kinesin protein and localizes to the nucleus,where it is required for the male meiotic cytokinesis after telophase Ⅱ.We further substantiated that MS1 colocalizes with microtubules and is essential for cell plate formation in soybean male gametogenesis through immunostaining.Both ms1 and CRISPR/Cas9 knockout mutants show complete male sterility but are otherwise phenotypically normal,making them perfect tools for producing hybrid seeds.The identification of MS1 has the practical potential for assembling the sterility system and speeding up hybrid soybean breeding.展开更多
Microtubules play a central role in cytoskeletal changes during neuronal development and maintenance.Microtubule dynamics is essential to polarity and shape transitions underlying neural cell division,differentiation,...Microtubules play a central role in cytoskeletal changes during neuronal development and maintenance.Microtubule dynamics is essential to polarity and shape transitions underlying neural cell division,differentiation,motility,and maturation.Kinesin superfamily protein 2A is a member of human kinesin 13 gene family of proteins that depolymerize and destabilize microtubules.In dividing cells,kinesin superfamily protein 2A is involved in mitotic progression,spindle assembly,and chromosome segregation.In postmitotic neurons,it is required for axon/dendrite specification and extension,neuronal migration,connectivity,and survival.Humans with kinesin superfamily protein 2A mutations suffer from a variety of malformations of cortical development,epilepsy,autism spectrum disorder,and neurodegeneration.In this review,we discuss how kinesin superfamily protein 2A regulates neuronal development and function,and how its deregulation causes neurodevelopmental and neurological disorders.展开更多
In higher plants, the preprophase band （PPB） of microtubules （MTs） forecasts the cell division site prior to mitosis and specifies the organization of MTs into a bipolar prophase spindle surrounding the nucleus. H...In higher plants, the preprophase band （PPB） of microtubules （MTs） forecasts the cell division site prior to mitosis and specifies the organization of MTs into a bipolar prophase spindle surrounding the nucleus. However, the mechanisms governing this PPB-dependent establishment of bipolarity are unclear. Here, we present evidence from live cell imaging studies that suggest a role for the MTs bridging the PPB and the prophase nucleus in mediating this function. Results from drug treatments, along with genetic evidence from null kinesin plants, suggest that these MTs contribute to the bipolarity, orientation, and position of the prophase spindle. Specifically, the absence of these bridge MTs is associated with lack of bipolarity, while non-uniform distributions of bridge MTs correlate with prophase spindle migration, deformation, and enhanced bipolarity toward the region of highest bridge MT density. This behavior does not require actomyosin-based forces, and is enhanced by suppressing MT dynamics with taxol. These observations occur during late prophase, and are coincident with the gradual closing of annular spindle poles. Based on these data, we describe a hypothetical mechanism for bridge MT-dependent organization of prophase spindles.展开更多
文摘The Arabidopsis FRA1 kinesin contributes to the organization of cellulose microfibrils through an unknown mechanism. The cortical localization of this kinesin during interphase raises the possibility that it transports cell wallrelated cargoes along cortical microtubules that either directly or indirectly influence cellulose microfibril patterning. To determine whether FRA1 is an authentic motor protein, we combined bulk biochemical assays and single molecule fluorescence imaging to analyze the motor properties of recombinant, GFP-tagged FRA1 containing the motor and coiled-coil domains （designated as FRAI（707）-GFP）. We found that FRAI（707）-GFP binds to microtubules in an ATP-dependent manner and that its ATPase activity is dramatically stimulated by the presence of microtubules. Using single molecule studies, we found that FRAI（707）-GFP moves processively along microtubule tracks at a velocity of about 0.4 μm s-1. In addition, we found that FRAI（707）-GFP is a microtubule plus-end-directed motor and that it moves along microtubules as a dimer. Interestingly, our single molecule analysis shows that the processivity of FRAI（707）-GFP is at least twice the processivity of conventional kinesin, making FRA1 the most processive kinesin to date. Together, our data show that FRA1 is a bona fide motor protein that has the potential to drive Iong-distance transport of cargo along cortical microtubules.
文摘Entosis, a ceU-in-ceU process, has been implicated in the formation of aneuploidy associated with an aberrant cell division control. Microtubule plus-end-tracking protein TI P150 facilitates the loading of MCAK onto the microtubule plus ends and orchestrates micro- tubule plus-end dynamics during cell division. Here we show that TIP150 cooperates with MCAK to govern entosis via a regulatory cir- cuitry that involves Aurora A-mediated phosphorylation of MCAK. Our biochemical analyses show that MCAK forms an intra-molecular association, which is essential for TIP150 binding. Interestingly, Aurora A-mediated phosphorylation of MCAK modulates its intra-mo- lecular association, which perturbs the MCAK-TI P150 interaction in vitro and inhibits entosis in vivo. To probe if MCAK-TIP150 inter- action regulates microtubule plasticity to affect the mechanical properties of ceUs during entosis, we used an optical trap to measure the mechanical rigidity of live MCF7 ceils. We find that the MCAK cooperates with TIP150 to promote microtubule dynamics and modulate the mechanical rigidity of the cells during entosis. Our results show that a dynamic interaction of MCAK-TI P150 orchestrated by Aurora A-mediated phosphorylation governs entosis via regulating microtubule plus-end dynamics and cell rigidity. These data reveal a previously unknown mechanism of Aurora A regulation in the control of microtubule plasticity during ceU-in-ceU pro- cesses.
文摘AIM: To examine the effect of the potential interaction between KIF1 B 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. Two single nucleotide polymorphisms(SNPs) of KIF1B(rs17401966 and rs3748578) were chosen for the current study. All subjects were genotypedusing a Taq Man real-time polymerase chain reaction. Multiplicative and additive logistic regression models were used to evaluate various gene-environment interactions.RESULTS: Smoking, frequent consumption of raw freshwater fish, hepatitis B virus(HBV) infection, and a family history of HCC were important risk factors for HCC in this population. Chronic infection with HBV was the most important environmental risk factor for HCC [odds ratio(OR) = 12.02; 95% confidence interval(95%CI): 6.02-24.00]. No significant association was found between the KIF1 B variants alone and the risk of HCC. Nevertheless, a significant additive effect modification was observed between rs17401966 and alcohol consumption(P for additive interaction = 0.0382). Compared with non-drinkers carrying either the AG or GG genotype of rs17401966, individuals classified as alcohol consumers with the AA genotype of rs17401966 had a significantly increased risk of HCC(OR = 2.36; 95%CI: 1.49-3.74).CONCLUSION: The gene-environment interaction between the KIF1 B rs17401966 variant and alcohol consumption may contribute to the development of HCC in Chinese individuals.
基金supported by the National Natural Science Foundation of China(32072084,31871648,and 31971969)。
文摘Male sterility is an essential trait in hybrid seed production,especially for monoclinous and autogamous food crops.Soybean male-sterile ms1 mutant has been known for more than 50 years and could be instrumental in making hybrid seeds.However,the gene responsible for the male-sterile phenotype has remained unknown.Here,we report the map-based cloning and characterization of the MS1 gene in soybean.MS1 encodes a kinesin protein and localizes to the nucleus,where it is required for the male meiotic cytokinesis after telophase Ⅱ.We further substantiated that MS1 colocalizes with microtubules and is essential for cell plate formation in soybean male gametogenesis through immunostaining.Both ms1 and CRISPR/Cas9 knockout mutants show complete male sterility but are otherwise phenotypically normal,making them perfect tools for producing hybrid seeds.The identification of MS1 has the practical potential for assembling the sterility system and speeding up hybrid soybean breeding.
基金Fund for Scientific Research(FNRS)PDR T0236.20FNRS-Exellence of Science 30913351FNRS CDR J.0175.23(to FT)。
文摘Microtubules play a central role in cytoskeletal changes during neuronal development and maintenance.Microtubule dynamics is essential to polarity and shape transitions underlying neural cell division,differentiation,motility,and maturation.Kinesin superfamily protein 2A is a member of human kinesin 13 gene family of proteins that depolymerize and destabilize microtubules.In dividing cells,kinesin superfamily protein 2A is involved in mitotic progression,spindle assembly,and chromosome segregation.In postmitotic neurons,it is required for axon/dendrite specification and extension,neuronal migration,connectivity,and survival.Humans with kinesin superfamily protein 2A mutations suffer from a variety of malformations of cortical development,epilepsy,autism spectrum disorder,and neurodegeneration.In this review,we discuss how kinesin superfamily protein 2A regulates neuronal development and function,and how its deregulation causes neurodevelopmental and neurological disorders.
基金This work was funded by grants from the National Science Foundation, the United States Department of Agriculture and Department of Energy. J.C.A. was supported by a National Science Foundation training grant.We thank D. Fisher for critical reading ofthe manuscript, T. Hashimoto for the generous gift of GFP：TUB6, and the Salk Institute Genomic Analysis Laboratory for providing the sequence-indexed Arabidopsis T-DNA insertion mutants. No conflict of interest declared.
文摘In higher plants, the preprophase band （PPB） of microtubules （MTs） forecasts the cell division site prior to mitosis and specifies the organization of MTs into a bipolar prophase spindle surrounding the nucleus. However, the mechanisms governing this PPB-dependent establishment of bipolarity are unclear. Here, we present evidence from live cell imaging studies that suggest a role for the MTs bridging the PPB and the prophase nucleus in mediating this function. Results from drug treatments, along with genetic evidence from null kinesin plants, suggest that these MTs contribute to the bipolarity, orientation, and position of the prophase spindle. Specifically, the absence of these bridge MTs is associated with lack of bipolarity, while non-uniform distributions of bridge MTs correlate with prophase spindle migration, deformation, and enhanced bipolarity toward the region of highest bridge MT density. This behavior does not require actomyosin-based forces, and is enhanced by suppressing MT dynamics with taxol. These observations occur during late prophase, and are coincident with the gradual closing of annular spindle poles. Based on these data, we describe a hypothetical mechanism for bridge MT-dependent organization of prophase spindles.
