The University of Tokyo · Biochemistry, Genetics and Molecular Biology
Professor Daiju Kitagawa's research lab focuses on the molecular mechanisms underlying centriole biogenesis, centrosome function, and their roles in cell division and development. The lab investigates key regulatory proteins such as Plk4, STIL, and CPAP, exploring how their dynamic interactions control centriole duplication, length regulation, and structural symmetry. Using advanced imaging techniques, structural biology, and cell biological approaches, the lab aims to decipher the self-organization principles of centriolar components and their implications in human diseases like microcephaly and cancer.
Figures are computed from collected data and may differ slightly.
The centriole, and the related basal body, is an ancient organelle characterized by a universal 9-fold radial symmetry and is critical for generating cilia, flagella, and centrosomes. The mechanisms directing centriole formation are incompletely understood and represent a fundamental open question in biology. Here, we demonstrate that the centriolar protein SAS-6 forms rod-shaped homodimers that interact through their N-terminal domains to form oligomers. We establish that such oligomerization i
Ultraviolet (UV) irradiation stimulates stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), which is a member of the mitogen-activated protein kinase (MAPK) superfamily and implicated in stress-induced apoptosis. UV also induces the activation of another MAPK member, extracellular signal-regulated kinase (ERK), which is typically involved in a growth-signaling cascade. However, the UV-induced signaling pathway leading to ERK activation, together with the physiological role, has r
Patients with MCPH (autosomal recessive primary microcephaly) exhibit impaired brain development, presumably due to the compromised function of neuronal progenitors. Seven MCPH loci have been identified, including one that encodes centrosome protein 4.1 associated protein (CPAP; also known as centromere protein J, CENPJ). CPAP is a large coiled-coil protein enriched at the centrosome, a structure that comprises two centrioles and surrounding pericentriolar material (PCM). CPAP depletion impairs
The number of centrioles is tightly controlled to ensure bipolar spindle assembly, which is a prerequisite to maintain genome integrity. However, our understanding of the fundamental principle that governs the formation of a single procentriole per parental centriole is incomplete. Here, we show that the local restriction of Plk4, a master regulator of the procentriole formation, is achieved by a bimodal interaction of STIL with Plk4. We demonstrate that the conserved short coiled-coil region of
In each cell cycle, centrioles are duplicated to produce a single copy of each preexisting centriole. At the onset of centriole duplication, the master regulator Polo-like kinase 4 (Plk4) undergoes a dynamic change in its spatial pattern around the preexisting centriole, forming a single duplication site. However, the significance and mechanisms of this pattern transition remain unknown. Using super-resolution imaging, we found that centriolar Plk4 exhibits periodic discrete patterns resembling
Several decades of centriole research have revealed the beautiful symmetry present in these microtubule-based organelles, which are required to form centrosomes, cilia and flagella in many eukaryotes. Centriole architecture is largely conserved across most organisms; however, individual centriolar features such as the central cartwheel or microtubule walls exhibit considerable variability when examined with finer resolution. In this paper, we review the ultrastructural characteristics of centrio
Mounting experimental evidence shows that non-coding RNAs (ncRNAs) serve a wide variety of biological functions. Recent studies suggest that a part of ncRNAs are critically important for supporting the structure of subcellular architectures. Here, we summarize the current literature demonstrating the role of ncRNAs and RNA-binding proteins in regulating the assembly of mitotic apparatus, especially focusing on centrosomes, kinetochores, and mitotic spindles.
During oogenesis, two successive meiotic cell divisions occur without functional centrosomes because of the inactivation and subsequent elimination of maternal centrosomes during the diplotene stage of meiosis I. Despite being a conserved phenomenon in most metazoans, the means by which this centrosome behavior is controlled during female meiosis remain elusive. Here, we conducted a targeted RNAi screening in the Caenorhabditis elegans gonad to identify novel regulators of centrosome behavior du
<i>CHAMP1</i> encodes a protein regulating kinetochore-microtubule attachment and chromosome segregation. These data strongly support that <i>CHAMP1</i> mutations cause ID, and suggest that CHAMP1 is critical for progression of cytokinesis and maintenance of centrosome number.
Intellectual disability (ID) is one of neurodevelopmental disorders characterized by serious defects in both intelligence and adaptive behavior. Although it has been suggested that genetic aberrations associated with the process of cell division underlie ID, the cytological evidence for mitotic defects in actual patient's cells is rarely reported. Here, we report a novel mutation in the STARD9 (also known as KIF16A) gene found in a patient with severe ID, characteristic features, epilepsy, acqui
SUMMARY In each cell cycle, centrioles are duplicated to produce a single copy of each pre-existing centriole. At the onset of centriole duplication, the master regulator Polo-like kinase 4 (Plk4) undergoes a dynamic change in its spatial pattern on the periphery of the pre-existing centriole, forming a single duplication site. However, the significance and mechanisms of this pattern transition remain largely unknown. Using super-resolution imaging, we found that centriolar Plk4 exhibits periodi
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