研究者業績

堅田 利明

Toshiaki Katada

基本情報

所属
武蔵野大学 薬学部 分子細胞生物学教室 教授
学位
薬学博士(北海道大学)

J-GLOBAL ID
200901067265815109
researchmap会員ID
1000161566

学歴

 2

論文

 20
  • Miharu Maeda, Toshiaki Katada, Kota Saito
    JOURNAL OF CELL BIOLOGY 216(6) 1731-1743 2017年6月  査読有り
    Mammalian endoplasmic reticulum (ER) exit sites export a variety of cargo molecules including oversized cargoes such as collagens. However, the mechanisms of their assembly and organization are not fully understood. TAN GO1L is characterized as a collagen receptor, but the function of TAN GO1S remains to be investigated. Here, we show that direct interaction between both isoforms of TAN GO1 and Sec16 is not only important for their correct localization but also critical for the organization of ER exit sites. The depletion of TAN GO1 disassembles COPII components as well as membrane-bound ER-resident complexes, resulting in fewer functional ER exit sites and delayed secretion. The ectopically expressed TAN GO1 C-terminal domain responsible for Sec16 binding in mitochondria is capable of recruiting Sec16 and other COPII components. Moreover, TAN GO1 recruits membrane-bound macromolecular complexes consisting of cTAGE5 and Sec12 to the ER exit sites. These data suggest that mammalian ER exit sites are organized by TAN GO1 acting as a scaffold, in cooperation with Sec16 for efficient secretion.
  • Miharu Maeda, Kota Saito, Toshiaki Katada
    MOLECULAR BIOLOGY OF THE CELL 27(17) 2688-2696 2016年9月  査読有り
    Collagens synthesized within the endoplasmic reticulum (ER) are too large to fit in conventional COPII-coated transport vesicles; thus their export from the ER requires specialized factors. TANGO1 (L) is an integral membrane protein that binds to collagen and the coatomer of vesicles and is necessary for collagen secretion from the ER. Here we characterized the short isoform of TANGO1 (TANGO1S), lacking the collagen-binding domain, and found that it was independently required for collagen export from the ER. Moreover, we found that each of the TANGO1 isoforms forms a stable protein complex with factors involved in collagen secretion: TANGO1L/cTAGE5/Sec12 (900 kDa) and TANGO1S/cTAGE5/Sec12 (700 kDa). Of interest, TANGO1S and TANGO1L seemed to be interchangeable in exporting collagen from the ER. Our results suggest that mammalian ER exit sites possess two different-sized membrane-bound macromolecular complexes that specifically function in large-cargo export from the ER.
  • Tomoya Tanabe, Miharu Maeda, Kota Saito, Toshiaki Katada
    MOLECULAR BIOLOGY OF THE CELL 27(13) 2008-2013 2016年7月  査読有り
    Two independent functions of cTAGE5 have been reported in collagen VII export from the endoplasmic reticulum (ER). cTAGE5 not only forms a cargo receptor complex with TANGO1, but it also acts as a scaffold to recruit Sec12, a guanine-nucleotide exchange factor for Sar1 GTPase, to ER exit sites. However, the relationship between the two functions remains unclear. Here we isolated point mutants of cTAGE5 that lost Sec12-binding ability but retained binding to TANGO1. Although expression of the mutant alone could not rescue the defects in collagen VII secretion mediated by cTAGE5 knockdown, coexpression with Sar1, but not with the GTPase-deficient mutant, recovered secretion. The expression of Sar1 alone failed to rescue collagen secretion in cTAGE5-depleted cells. Taken together, these results suggest that two functionally irreplaceable and molecularly separable modules in cTAGE5 are both required for collagen VII export from the ER. The recruitment of Sec12 by cTAGE5 contributes to efficient activation of Sar1 in the vicinity of ER exit sites. In addition, the GTPase cycle of Sar1 appears to be responsible for collagen VII exit from the ER.
  • Yasunobu Nagata, Kenji Kontani, Terukazu Enami, Keisuke Kataoka, Ryohei Ishii, Yasushi Totoki, Tatsuki R. Kataoka, Masahiro Hirata, Kazuhiro Aoki, Kazumi Nakano, Akira Kitanaka, Mamiko Sakata-Yanagimoto, Sachiko Egami, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Yusuke Shiozawa, Tetsuichi Yoshizato, Hiromichi Suzuki, Ayana Kon, Kenichi Yoshida, Yusuke Sato, Aiko Sato-Otsubo, Masashi Sanada, Wataru Munakata, Hiromi Nakamura, Natsuko Hama, Satoru Miyano, Osamu Nureki, Tatsuhiro Shibata, Hironori Haga, Kazuya Shimoda, Toshiaki Katada, Shigeru Chiba, Toshiki Watanabe, Seishi Ogawa
    BLOOD 127(5) 596-604 2016年2月  査読有り
    Adult T-cell leukemia/lymphoma (ATLL) is a distinct form of peripheral T-cell lymphoma with poor prognosis, which is caused by the human T-lymphotropic virus type 1 (HTLV-1). In contrast to the unequivocal importance of HTLV-1 infection in the pathogenesis of ATLL, the role of acquired mutations in HTLV-1 infected T cells has not been fully elucidated, with a handful of genes known to be recurrently mutated. In this study, we identified unique RHOA mutations in ATLL through whole genome sequencing of an index case, followed by deep sequencing of 203 ATLL samples. RHOA mutations showed distinct distribution and function from those found in other cancers. Involving 15% (30/203) of ATLL cases, RHOA mutations were widely distributed across the entire coding sequence but almost invariably located at the guanosine triphosphate (GTP)-binding pocket, with Cys16Arg being most frequently observed. Unexpectedly, depending on mutation types and positions, these RHOA mutants showed different or even opposite functional consequences in terms of GTP/guanosine diphosphate (GDP)-binding kinetics, regulation of actin fibers, and transcriptional activation. The Gly17Val mutant did not bind GTP/GDP and act as a dominant negative molecule, whereas other mutants (Cys16Arg and Ala161Pro) showed fast GTP/GDP cycling with enhanced transcriptional activation. These findings suggest that both loss-and gain-of-RHOA functions could be involved in ATLL leukemogenesis. In summary, our study not only provides a novel insight into the molecular pathogenesis of ATLL but also highlights a unique role of variegation of heterologous RHOA mutations in human cancers.
  • Kota Saito, Toshiaki Katada
    CELLULAR AND MOLECULAR LIFE SCIENCES 72(19) 3709-3720 2015年10月  査読有り
    Cargo proteins exported from the endoplasmic reticulum to the Golgi apparatus are typically transported in coat protein complex II (COPII)-coated vesicles of 60-90 nm diameter. Several cargo molecules including collagens and chylomicrons form structures that are too large to be accommodated by these vesicles, but their secretion still requires COPII proteins. Here, we first review recent progress on large cargo secretions derived especially from animal models and human diseases, which indicate the importance of COPII proteins. We then discuss the recent isolation of specialized factors that modulate the process of COPII-dependent cargo formation to facilitate the exit of large-sized cargoes from the endoplasmic reticulum. Based on these findings, we propose a model that describes the importance of the GTPase cycle for secretion of oversized cargoes. Next, we summarize reports that describe the structures of COPII proteins and how these results provide insight into the mechanism of assembly of the large cargo carriers. Finally, we discuss what issues remain to be solved in the future.

資格・免許

 1
  • 件名
    薬剤師免許
    年月日
    1976