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The interaction between KIF21A and KANK1 regulates dendritic morphology and synapse plasticity in neurons

Neural Regeneration Research 2025年第1期20卷 209-223页

作者： Shi-Yan Sun Lingyun Nie Jing Zhang Xue Fang Hongmei Luo chuanhai fu Zhiyi Wei Ai-Hui Tang Hefei National Research Center for Physical Sciences at the Microscale CAS Key Laboratory of Brain Function and DiseaseMinistry of Education Key Laboratory for Membrane-less Organelles and Cellular DynamicsDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui ProvinceChina Institute of Artificial Intelligence Hefei Comprehensive National Science CenterHefeiAnhui ProvinceChina CAS Center for Excellence in Molecular Cell Sciences Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui ProvinceChina Department of Neurobiology School of Life SciencesSouthern University of Science and TechnologyShenzhenGuangdong ProvinceChina Brain Research Center Southern University of Science and TechnologyShenzhenGuangdong ProvinceChina

Morphological alterations in dendritic spines have been linked to changes in functional communication between neurons that affect learning and ***-4 KIF21A helps organize the microtubule-actin network at the cell cortex by interacting with KANK1;however,whether KIF21A modulates dendritic structure and function in neurons remains *** this study,we found that KIF21A was distributed in a subset of dendritic spines,and that these KIF21A-positive spines were larger and more structurally plastic than KIF21A-negative ***,the interaction between KIF21A and KANK1 was found to be critical for dendritic spine morphogenesis and synaptic *** of either KIF21A or KANK1 inhibited dendritic spine morphogenesis and dendritic branching,and these deficits were fully rescued by coexpressing full-length KIF21A or KANK1,but not by proteins with mutations disrupting direct binding between KIF21A and KANK1 or binding between KANK1 and *** down KIF21A in the hippocampus of rats inhibited the amplitudes of long-term potentiation induced by high-frequency stimulation and negatively impacted the animals’cognitive *** together,our findings demonstrate the function of KIF21A in modulating spine morphology and provide insight into its role in synaptic function.

关键词： actin cytoskeleton dendrite KANK1 KIF21A microtubule spine morphology spine synaptic plasticity talin1

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The concerted actions of Tipl/CLIP-170, Klp5/Kinesin-8, and Alpl4/XMAP215 regulate microtubule catastrophe at the cell end

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Journal of Molecular Cell Biology 2019年第11期11卷 956-966页

作者： Xiaojia Niu Fan Zheng chuanhai fu Division of Molecular&Cell Biophysics Hefei National Science Center for Physical SciencesUniversity of Science and Technology of ChinaHefeiAnhuiChina Chinese Academy of Sciences Center for Excellence in Molecular Cell Sciences School of Life SciencesUniversity of Science and Technology of ChinaHefeiAnhuiChina Anhui Key Laboratory for Cellular Dynamics&Chemical Biology University of Science and Technology of ChinaHefeiChina

Spatial regulation of microtubule catastrophe is important for controlling microtubule length and consequently contributes to the proper establishment of cell polarity and cell ***+TIP proteins including Tipl/CLIP-170,Klp5/Kinesin-8,and Alpl4/XMAP215 reside at microtubule plus ends to regulate microtubule *** the fission yeast Schizosaccharomyces pombe,Tipi and Alpl4 serve as microtubule-stabilizing factors,while Klp5 functions oppositely as a catastrophe-promoting *** that Tipi has been shown to play a key role in restricting microtubule catastrophe to the cell end,how Tipi fulfills the role remains to be *** live-cell microscopy,we showed that the absence of Tip i impairs the localization of both Klp5 and Alpl4 at microtubule plus ends,but the absence of Klp5 prolongs the residence time of Tipi at microtubule plus *** further revealed that Klp5 accumulates behind Tip i at microtubule plus ends in a Tipl-dependent *** addition,artificially tethering Klp5 to microtubule plus ends promotes premature microtubule catastrophe,while tethering Alpl4 to microtubule plus ends in the cells lacking Tipi rescues the phenotype of short *** findings establish that Tipi restricts microtubule catastrophe to the cell end likely by spatially restricting the microtubule catastrophe activity of Klp5 and stabilizing Alpl4 at microtubule plus ***,the work demonstrates the orchestration of Tipi,Alpl4,and Klp5 in ensuring microtubule catastrophe at the cell end.

关键词： microtubule microtubule catastrophe kinesin-8 Tipi Alpl4

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Alp7-Mtol and Alpl4 synergize to promote interphase microtubule regrowth from the nuclear envelope

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Journal of Molecular Cell Biology 2019年第11期11卷 944-955页

作者： Wenyue Liu Fan Zheng Yucai Wang chuanhai fu Division of Molecular and Cell Biophysics Hefei National Science Center for Physical SciencesUniversity of Science and Technology of ChinaHefeiChina Chinese Academy of Sciences Center for Excellence in Molecular Cell Sciences School of Life SciencesUniversity of Science and Technology of ChinaHefeiChina Anhui Key Laboratory for Cellular Dynamics and Chemical Biology University of Science and Technology of ChinaHefeiChina School of Life Sciences University of Science and Technology of ChinaHefeiChina

Microtubules grow not only from the centrosome but also from various noncentrosomal microtubule-organizing centers(MTOCs),including the nuclear envelope(NE)and pre-existing *** evolutionarily conserved proteins Mtol/CDK5RAP2 and Alpl4/TOG/XMAP215 have been shown to be involved in promoting microtubule ***,it has remained elusive as to how the microtubule nucleation promoting factors are specified to various noncentrosomal MTOCs,particularly the NE,and how these proteins coordinate to organize microtubule ***,we demonstrate that in the fission yeast Schizosaccharomyces pombe,efficient interphase microtubule growth from the NE requires Alp7/TACC,Alpl4/TOG/XMAP215,and Mtol/*** absence of Alp7,A lp l4 t or Mtol compromises microtubule regrowth on the NE in cells undergoing microtubule *** further demonstrate that Alp7 and Mtol interdependently localize to the NE in cells without microtubules and that A lp l4 localizes to the NE in an Alp7 and Mtol-dependent *** Mtol to the NE in cells lacking Alp7 partially restores microtubule number and the efficiency of microtubule generation from the ***,our study delineates that Alp7,A lpl4,and Mtol work in concert to regulate interphase microtubule regrowth on the NE.

关键词： microtubule microtubule nucleation nuclear envelope microtubule-associated protein fission yeast

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Fission yeast cells mix parental mitochondria in a progressive manner during meiosis

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Journal of Molecular Cell Biology 2022年第11期14卷 62-75页

作者： Daqiang Wu Yongkang Chu Wenfan Wei Ling Liu chuanhai fu Ministry of Education Key Laboratory for Cellular Dynamics Hefei National Laboratory for Physical Sciences at the MicroscaleDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230027China Anhui Province Key Laboratory of Research&Development of Chinese Medicine College of Integrated Chinese and Western MedicineAnhui University of Chinese MedicineHefei 230038China

Mitochondria in many fungi are inherited uniparentally during meiosis. It has remained unclear whether parental mitochondria in the fission yeast Schizosaccharomyces pombe are inherited uniparentally or biparentally. Here, we assessed the mixing of parental mitochondria carefully by live-cell microscopy and developed an algorithm to determine the degree of mitochondrial mixing in a quantitative manner. We found that parental mitochondria in fission yeast cells were mixed progressively as meiosis progressed. Moreover, we established that mitochondrial fission and the size of the conjugation neck are the limiting factors in restricting the mixing of parental mitochondria. We further employed a combination of quantitative polymerase chain reaction, fluorescent live-cell microscopy, and transmission electron microscopy approaches to examine the mitochondrial inheritance of progeny cells derived from a cross between wild-type and Rho0 (mitochondrial DNA absent) cells. The results show that all progeny cells of the cross carry mitochondrial DNA. Hence, our data support the model in which parental mitochondria in the fission yeast S. pombe are inherited biparentally during meiosis.

关键词： mitochondria mitochondrial inheritance mitochondrial fission fission yeast

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Protein kinase TTK interacts and co-localizes with CENP-E to the kinetochore of human cells

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Chinese Science Bulletin 2002年第23期47卷 2005-2009页

作者： Jie Zhang chuanhai fu Yong Miao Zhen Dou Xuebiao Yao Univ Sci & Technol China Lab Cell Dynam Hefei 230027 Peoples R China

Spindle checkpoint is an important biochemical signaling cascade during mitosis which monitors the fidelity of chromosome segregation, and is mediated by protein kinases Mpsl and Bubl/BubRl. Our recent studies show that kinesin-related motor protein CENP-E interacts with BubRl and participates in spindle checkpoint signaling. To elucidate the molecular mechanisms underlying spindle checkpoint signaling, we carried out proteomic dissection of human cell kinetochore and revealed protein kinase TTK, human homologue of yeast Mpsl. Our studies show that TTK is localized to the kinetochore of human cells, and interacts with CENP-E, suggesting that TTK may play an important role in chromosome segregation during mitosis.

关键词： spindle checkpoint TTK protein kinase CENP-E kinetochore.

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A novel genome-wide full-length kinesin prediction analysis reveals additional mammalian kinesins

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Chinese Science Bulletin 2006年第15期51卷 1836-1847页

作者： XUE Yu LIU Dan fu chuanhai DOU Zhen ZHOU Qing YAO Xuebiao Laboratory of Cellular Dynamics University of Science & Technology of China/Hefei National Laboratory Hefei 230027 China College of Agriculture Zhejiang University Hangzhou 310003 China

Kinesin superfamily of microtubule- based motor orchestrates a variety of cellular proc- esses. Recent availability of mammalian genomes has enabled analyses of kinesins on the whole ge- nome. Here we present a novel full-length kinesin prediction program (FKPP) for mammalian kinesin gene discovery based on a comparative genomics approach. Contrary to previous predictions of 94 kinesins, we identify a total of 134 potentially kinesin genes from mammalian genomes, including 45 from mouse, 45 from rat and 44 from human. In addition, FKPP synthesizes 25 potentially full-length mam- malian kinesins based on the partial sequences in the database. Surprisingly, FKPP reveals that full-length human CENP-E contains 2701 aa rather than 2663 aa in the database. Experimentation using sequence specific antibody and cDNA sequencing of human CENP-E validates the accuracy of FKPP. Given the remarkable computing efficiency and accuracy of FKPP, we reclassify the mammalian kinesin super- family. Since current databases contain many in- complete sequences, FKPP may provide a novel approach for molecular delineation of kinesins and other protein families.

关键词：驱动蛋白基因组 CENP-E FKPP

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Structural insights reveal the specific recognition of meiRNA by the Mei2 protein

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Journal of Molecular Cell Biology 2022年第5期14卷 27-42页

作者： Siyuan Shen Yanze jian Zhaokui Cai fudong Li Mengqi Lv Yongrui Liu Jihui Wu chuanhai fu Yunyu Shi School of Life Sciences Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230026China MOE key Laboratory for Cellular Dynamics University of Science&Technology of ChinaHefei 230026China Key Laboratory of RNA Biology Institute of BiophysicsChinese Academy of SciencesBeijing 100101China

In the fission yeast Schizosaccharomyces pombe,Mei2,an RNA-binding protein essential for entry into meiosis,regulates meiosis ***2 binds to a specific non-coding RNA species,meiRNA,and accumulates at the sme2 gene locus,which encodes *** research has shown that the Mei2 C-terminal RNA recognition motif(RRM3)physically interacts with the meiRNA 5'region in vitro and stimulates meiosis in ***,the underlying mechanisms still remain *** first employed an in vitro crosslinking and immunoprecipitation sequencing(CLIP-seq)assay and demonstrated a preference for U-rich motifs of meiRNA by Mei2 *** then solved the crystal structures of Mei2 RRM3 in the apo form and complex with an 8 mer RNA fragment,derived from meiRNA,as detected by in vitro *** results provide structural insights into the Mei2 RRM3-meiRNA complex and reveal that Mei2 RRM3 binds specifically to the Uuc(U)***,a structure-based Mei2 mutation,Mei2F644A causes defective karyogamy,suggesting an essential role of the RNA-binding ability of Mei2 in regulating meiosis.

关键词： Mei2 meiRNA meiosis RNA-binding protein crystallography

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The septin complex links the catenin complex to the actin cytoskeleton for establishing epithelial cell polarity

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Journal of Molecular Cell Biology 2021年第6期13卷 395-408页

作者： Xueying Wang Wenwen Wang Xiwei Wang Ming Wang Lijuan Zhu Fatima Garba chuanhai fu Barbara Zieger Xu Liu Xing Liu Xuebiao Yao MOE Key Laboratory for Membraneless Organelles&Cellular Dynamics and Hefei National Laboratory for Physical Sciences at the Microscale University of Science and Technology of ChinaHefei 230027China Keck Center for Organoids Plasticity Control AtlantaGA 30310USA Anhui Key Laboratory for Cellular Dynamics&Chemical Biology and CAS Center for Excellence in Molecular Cell Science Hefei 230027China Department of Pediatrics and Adolescent Medicine Division of Pediatric Hematology and OncologyMedical CenterFaculty of MedicineUniversity of Freiburg79106 FreiburgGermany

Cell polarity is essential for spatially regulating of physiological processes in metazoans by which hormonal stimulation‒secretion coupling is precisely coupled for tissue homeostasis and organ ***,the molecular mechanisms underlying epithelial cell polarity establishment remain ***,we show that septin cytoskeleton interacts with catenin complex to organize a functional domain to separate apical from basal membranes in polarized epithelial *** polarized epithelial cell monolayer as a model system with transepithelial electrical resistance as functional readout,our studies show that septins are essential for epithelial cell *** proteomic analyses discovered a novel septin‒catenin complex during epithelial cell *** functional relevance of septin‒catenin complex was then examined in three-dimensional(3D)culture in which suppression of septins resulted in deformation of apical lumen in cysts,a hallmark seen in polarity-deficient 3D cultures and ***,septin cytoskeleton stabilizes the association of adherens catenin complex with actin cytoskeleton,and depletion or disruption of septin cytoskeleton liberates adherens junction and polarity complexes into the ***,these findings reveal a previously unrecognized role for septin cytoskeleton in the polarization of the apical‒basal axis and lumen formation in polarized epithelial cells.

关键词： septin cytoskeleton cell polarity adherens junction epithelial cells

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Mcp1p tracks microtubule plus ends to destabilize microtubules at cell tips

Mcp1p tracks microtubule plus ends to destabilize microtubul...

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第九届中国模式真菌研讨会

作者： Fan Zheng Tianpeng Li chuanhai fu School of Life Sciences University of Science and Technology of China Department of Biochemistry The University of Hong Kong

Microtubule plus ends are dynamically regulated by a wide variety of proteins for performing diverse cellular ***,we show that the fission yeast Schizosaccharomyces pombe uncharacterized protein mcp1p is a microtubule

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Csi1p recruits alp7p/TACC to the spindle pole bodies for bipolar spindle formation

Csi1p recruits alp7p/TACC to the spindle pole bodies for bip...

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第九届中国模式真菌研讨会

作者： Fan Zheng Tianpeng Li chuanhai fu School of Life Sciences University of Science and Technology of China Department of Biochemistry The University of Hong Kong

Accurate chromosome segregation requires timely bipolar spindle formation during *** transforming acidic coiled-coil(TACC)family proteins and the ch-TOG family proteins are key players in bipolar spindle *** form a co...

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