Kai Jiang
Utrecht University
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Publication
Featured researches published by Kai Jiang.
Current Biology | 2012
Kai Jiang; Grischa Toedt; Susana Montenegro Gouveia; Norman E. Davey; Shasha Hua; Babet van der Vaart; Ilya Grigoriev; Jesper Larsen; Lotte B. Pedersen; Karel Bezstarosti; Mariana Lince-Faria; Jeroen Demmers; Michel O. Steinmetz; Toby J. Gibson; Anna Akhmanova
Microtubule plus-end tracking proteins (+TIPs) are structurally and functionally diverse factors that accumulate at the growing microtubule plus-ends, connect them to various cellular structures, and control microtubule dynamics [1, 2]. EB1 and its homologs are +TIPs that can autonomously recognize growing microtubule ends and recruit to them a variety of other proteins. Numerous +TIPs bind to end binding (EB) proteins through natively unstructured basic and serine-rich polypeptide regions containing a core SxIP motif (serine-any amino acid-isoleucine-proline) [3]. The SxIP consensus sequence is short, and the surrounding sequences show high variability, raising the possibility that undiscovered SxIP containing +TIPs are encoded in mammalian genomes. Here, we performed a proteome-wide search for mammalian SxIP-containing +TIPs by combining biochemical and bioinformatics approaches. We have identified a set of previously uncharacterized EB partners that have the capacity to accumulate at the growing microtubule ends, including protein kinases, a small GTPase, centriole-, membrane-, and actin-associated proteins. We show that one of the newly identified +TIPs, CEP104, interacts with CP110 and CEP97 at the centriole and is required for ciliogenesis. Our study reveals the complexity of the mammalian +TIP interactome and provides a basis for investigating the molecular crosstalk between microtubule ends and other cellular structures.
Current Opinion in Cell Biology | 2011
Kai Jiang; Anna Akhmanova
Microtubule ends serve as sites of tubulin addition and removal, and at the same time play crucial roles in microtubule capture, stabilization and attachment to different cellular structures. Microtubule plus and minus-ends possess distinct structural and dynamic properties, and are recognized, bound and regulated by diverse factors. These include specific capping factors such as γ-tubulin, motors, such as plus-end and minus-end directed kinesins, highly specialized kinetochore-bound microtubule-associated proteins, and comet-making plus-end tracking proteins such as EB1 and its partners. Here, we provide an overview of microtubule tip-interacting proteins and the mechanisms responsible for their association with microtubule ends, and discuss the functional cross-talk between microtubule plus and minus-end binding factors.
Neuron | 2014
Kah Wai Yau; Sam F.B. van Beuningen; Inês Cunha-Ferreira; Bas M. C. Cloin; Eljo Y. van Battum; Lena Will; Philipp Schätzle; Roderick P. Tas; Jaap van Krugten; Eugene A. Katrukha; Kai Jiang; Phebe S. Wulf; Marina Mikhaylova; Martin Harterink; R. Jeroen Pasterkamp; Anna Akhmanova; Lukas C. Kapitein; Casper C. Hoogenraad
In neurons, most microtubules are not associated with a central microtubule-organizing center (MTOC), and therefore, both the minus and plus-ends of these non-centrosomal microtubules are found throughout the cell. Microtubule plus-ends are well established as dynamic regulatory sites in numerous processes, but the role of microtubule minus-ends has remained poorly understood. Using live-cell imaging, high-resolution microscopy, and laser-based microsurgery techniques, we show that the CAMSAP/Nezha/Patronin family protein CAMSAP2 specifically localizes to non-centrosomal microtubule minus-ends and is required for proper microtubule organization in neurons. CAMSAP2 stabilizes non-centrosomal microtubules and is required for neuronal polarity, axon specification, and dendritic branch formation in vitro and in vivo. Furthermore, we found that non-centrosomal microtubules in dendrites are largely generated by γ-Tubulin-dependent nucleation. We propose a two-step model in which γ-Tubulin initiates the formation of non-centrosomal microtubules and CAMSAP2 stabilizes the free microtubule minus-ends in order to control neuronal polarity and development.
EMBO Reports | 2009
Kai Jiang; Jianyu Wang; Jing Liu; Tarsha Ward; Linda Wordeman; Alec J. Davidson; Fengsong Wang; Xuebiao Yao
The microtubule (MT) cytoskeleton orchestrates the cellular plasticity and dynamics that underlie morphogenesis and cell division. Growing MT plus ends have emerged as dynamic regulatory machineries in which specialized proteins—called plus‐end tracking proteins (+TIPs)—bind to and control the plus‐end dynamics that are essential for cell division and migration. However, the molecular mechanisms underlying the plus‐end regulation by +TIPs at spindle and astral MTs have remained elusive. Here, we show that TIP150 is a new +TIP that binds to end‐binding protein 1 (EB1) in vitro and co‐localizes with EB1 at the MT plus ends in vivo. Suppression of EB1 eliminates the plus‐end localization of TIP150. Interestingly, TIP150 also binds to mitotic centromere‐associated kinesin (MCAK), an MT depolymerase that localizes to the plus end of MTs. Suppression of TIP150 diminishes the plus‐end localization of MCAK. Importantly, aurora B‐mediated phosphorylation disrupts the TIP150–MCAK association in vitro. We reason that TIP150 facilitates the EB1‐dependent loading of MCAK onto MT plus ends and orchestrates the dynamics at the plus end of MTs.
Journal of Biological Chemistry | 2011
Shasha Hua; Zhikai Wang; Kai Jiang; Yuejia Huang; Tarsha Ward; Lingli Zhao; Zhen Dou; Xuebiao Yao
Mitosis is an orchestration of dynamic interaction between chromosomes and spindle microtubules by which genomic materials are equally distributed into two daughter cells. Previous studies showed that CENP-U is a constitutive centromere component essential for proper chromosome segregation. However, the precise molecular mechanism has remained elusive. Here, we identified CENP-U as a novel interacting partner of Hec1, an evolutionarily conserved kinetochore core component essential for chromosome plasticity. Suppression of CENP-U by shRNA resulted in mitotic defects with an impaired kinetochore-microtubule attachment. Interestingly, CENP-U not only binds microtubules directly but also displays a cooperative microtubule binding activity with Hec1 in vitro. Furthermore, we showed that CENP-U is a substrate of Aurora-B. Importantly, phosphorylation of CENP-U leads to reduced kinetochore-microtubule interaction, which contributes to the error-correcting function of Aurora-B. Taken together, our results indicate that CENP-U is a novel microtubule binding protein and plays an important role in kinetochore-microtubule attachment through its interaction with Hec1.
Journal of Biological Chemistry | 2009
Kai Yuan; Na Li; Kai Jiang; Tongge Zhu; Yuda Huo; Chong Wang; Jing Lu; Andrew R. E. Shaw; Kelwyn Thomas; Jiancun Zhang; David J. Mann; Jian Liao; Changjiang Jin; Xuebiao Yao
Mitosis is an orchestration of dynamic interactions between spindle microtubules and chromosomes, which is mediated by protein structures that include the kinetochores, and other protein complexes present on chromosomes. PinX1 is a potent telomerase inhibitor in interphase; however, its function in mitosis is not well documented. Here we show that PinX1 is essential for faithful chromosome segregation. Deconvolution microscopic analyses show that PinX1 localizes to nucleoli and telomeres in interphase and relocates to the periphery of chromosomes and the outer plate of the kinetochores in mitosis. Our deletion analyses mapped the kinetochore localization domain of PinX1 to the central region and its chromosome periphery localization domain to the C terminus. Interestingly, the kinetochore localization of PinX1 is dependent on Hec1 and CENP-E. Our biochemical characterization revealed that PinX1 is a novel microtubule-binding protein. Our real time imaging analyses show that suppression of PinX1 by small interference RNA abrogates faithful chromosome segregation and results in anaphase chromatid bridges in mitosis and micronuclei in interphase, suggesting an essential role of PinX1 in chromosome stability. Taken together, the results indicate that PinX1 plays an important role in faithful chromosome segregation in mitosis.
Cell Research | 2007
Guosheng Fu; Xia Ding; Kai Yuan; Felix O. Aikhionbare; Jianhui Yao; Xin Cai; Kai Jiang; Xuebiao Yao
Chromosome segregation in mitosis is orchestrated by the interaction of the kinetochore with spindle microtubules. Our recent study shows that NEK2A interacts with MAD1 at the kinetochore and possibly functions as a novel integrator of spindle checkpoint signaling. However, it is unclear how NEK2A regulates kinetochore-microtubule attachment in mitosis. Here we show that NEK2A phosphorylates human Sgo1 and such phosphorylation is essential for faithful chromosome congression in mitosis. NEK2A binds directly to HsSgo1 in vitro and co-distributes with HsSgo1 to the kinetochore of mitotic cells. Our in vitro phosphorylation experiment demonstrated that HsSgo1 is a substrate of NEK2A and the phosphorylation sites were mapped to Ser14 and Ser507 as judged by the incorporation of 32P. Although such phosphorylation is not required for assembly of HsSgo1 to the kinetochore, expression of non-phosphorylatable mutant HsSgo1 perturbed chromosome congression and resulted in a dramatic increase in microtubule attachment errors, including syntelic and monotelic attachments. These findings reveal a key role for the NEK2A-mediated phosphorylation of HsSgo1 in orchestrating dynamic kinetochore-microtubule interaction. We propose that NEK2A-mediated phosphorylation of human Sgo1 provides a link between centromeric cohesion and spindle microtubule attachment at the kinetochores.
Journal of Biological Chemistry | 2009
Jing Liu; Zhikai Wang; Kai Jiang; Liangyu Zhang; Lingli Zhao; Shasha Hua; Feng Yan; Yong Yang; Dongmei Wang; Chuanhai Fu; Xia Ding; Zhen Guo; Xuebiao Yao
During cell division, chromosome segregation is governed by the interaction of spindle microtubules with the kinetochore. A dramatic remodeling of interpolar microtubules into an organized central spindle between the separating chromatids is required for the initiation and execution of cytokinesis. Central spindle organization requires mitotic kinesins, microtubule-bundling protein PRC1, and Aurora B kinase complex. However, the precise role of PRC1 in central spindle organization has remained elusive. Here we show that PRC1 recruits CLASP1 to the central spindle at early anaphase onset. CLASP1 belongs to a conserved microtubule-binding protein family that mediates the stabilization of overlapping microtubules of the central spindle. PRC1 physically interacts with CLASP1 and specifies its localization to the central spindle. Repression of CLASP1 leads to sister-chromatid bridges and depolymerization of spindle midzone microtubules. Disruption of PRC1-CLASP1 interaction by a membrane-permeable peptide abrogates accurate chromosome segregation, resulting in sister chromatid bridges. These findings reveal a key role for the PRC1-CLASP1 interaction in achieving a stable anti-parallel microtubule organization essential for faithful chromosome segregation. We propose that PRC1 forms a link between stabilization of CLASP1 association with central spindle microtubules and anti-parallel microtubule elongation.
FEBS Letters | 2007
Ya Liu; Xia Ding; Dongmei Wang; Hui Deng; Mingye Feng; Min Wang; Xue Yu; Kai Jiang; Tarsha Ward; Felix O. Aikhionbare; Zhen Guo; John G. Forte; Xuebiao Yao
Syntaxin and Munc18 are essential for regulated exocytosis in all eukaryotes. It was shown that Munc18 inhibition of neuronal syntaxin 1 can be overcome by CDK5 phosphorylation, indicating that structural change disrupts the syntaxin–Munc18 interaction. Here, we show that this phosphorylation promotes the assembly of Munc18b–syntaxin 3–SNAP25 tripartite complex and membrane fusion machinery SNARE. Using siRNAs to screen for genes required for regulated epithelial secretion, we identified the requirements of CDK5 and Munc18b in cAMP‐dependent gastric acid secretion. Biochemical characterization revealed that Munc18b bears a syntaxin 3‐selective binding site located at its most C‐terminal 53 amino acids. Significantly, the phosphorylation of Thr572 by CDK5 attenuates Munc18b–syntaxin 3 interaction and promotes formation of Munc18b–syntaxin 3–SNAP25 tripartite complex, leading to an assembly of functional Munc18b–syntaxin 3–SNAP25–VAMP2 membrane fusion machinery. Thus, our studies suggest a novel regulatory mechanism in which phosphorylation of Munc18b operates vesicle docking and fusion in regulated exocytosis.
Journal of Cell Science | 2016
Ivar Noordstra; Qingyang Liu; Wilco Nijenhuis; Shasha Hua; Kai Jiang; Matthijs Baars; Sanne Remmelzwaal; Maud Martin; Lukas C. Kapitein; Anna Akhmanova
ABSTRACT The microtubule cytoskeleton regulates cell polarity by spatially organizing membrane trafficking and signaling processes. In epithelial cells, microtubules form parallel arrays aligned along the apico–basal axis, and recent work has demonstrated that the members of CAMSAP/Patronin family control apical tethering of microtubule minus ends. Here, we show that in mammalian intestinal epithelial cells, the spectraplakin ACF7 (also known as MACF1) specifically binds to CAMSAP3 and is required for the apical localization of CAMSAP3-decorated microtubule minus ends. Loss of ACF7 but not of CAMSAP3 or its homolog CAMSAP2 affected the formation of polarized epithelial cysts in three-dimensional cultures. In short-term epithelial polarization assays, knockout of CAMSAP3, but not of CAMSAP2, caused microtubule re-organization into a more radial centrosomal array, redistribution of Rab11-positive (also known as Rab11A) endosomes from the apical cell surface to the pericentrosomal region and inhibition of actin brush border formation at the apical side of the cell. We conclude that ACF7 is an important regulator of apico–basal polarity in mammalian intestinal cells and that a radial centrosome-centered microtubule organization can act as an inhibitor of epithelial polarity. Highlighted Article: The spectraplakin ACF7 and microtubule minus-end-stabilizing protein CAMSAP3 cooperate in organizing non-centrosomal microtubule arrays in intestinal epithelial cells.