九州大学 生体防御医学研究所

下記の通り、Rachubinski先生によるセミナーを開催致します。

Rachubinski先生は、これまで細胞生物学領域：細胞内タンパク質の選別輸送、オルガネラ創成などの 研究分野を代表する独創的な研究を推進されてきています。特にペルオキシソームの形成制御やPPARなど核内レセプターの分子生理学では大きく貢献され、国際的にも非常に高く評価されておいでです。また、本領域研究の面白さに加えて自身のresearch philosophyやthe importance of training abroadなど、意見交換等と共に語って頂きます。 多くの方々のご来聴をお待ちしております。

演題

Defining molecular events of peroxisome biogenesis at the endoplasmic reticulum.

演者

Richard A. Rachubinski
Professor and Chair, Department of Cell Biology, University of Alberta, Canada

日時

2016年 9月28日（水）　Sep. 28 (Wed), 2016
15：30～17：30

場所

病院キャンパス内　総合研究棟1階 105 セミナー室
以下の地図の1番です。
（https://www.kyushu-u.ac.jp/f/28545/hospital_jp.pdf）

Seminar Room 105, 1F, Biomedical Research Station
No.1 on the following linked map.
（https://www.kyushu-u.ac.jp/f/28551/hospital_en.pdf）

要旨

Peroxisome proliferation occurs by two separate, yet complementary, pathways: de novo budding from the endoplasmic reticulum (ER) and division of existing peroxisomes.¹⁾ To date, the proteins and molecular mechanisms that govern the emergence of peroxisomes from the ER remain poorly characterized. In cells lacking peroxisomes, de novo synthesis starts with the recruitment of Pex19, a cytosolic chaperone, to aid in the formation of preperoxisomal vesicles (PPVs) containing peroxisomal membrane proteins. Little is known about how PPVs form other than the requirements for Pex19 and ATP hydrolysis. We have recently reported that two integral membrane peroxins (proteins required for peroxisome assembly) in Saccharomyces cerevisiae, Pex29 and Pex30, reside in distinct regions of the ER and associate with Rtn1, Rtn2 and Yop1, members of the reticulon family of proteins that influence ER morphology, to govern peroxisome emergence from the ER.²⁾ Using both in vivo and in vitro analyses, we have revealed that peroxisome proliferation is not restricted to the level of the peroxisome itself, but begins earlier at the ER.

Using a systems-level, multi-parameter quantitative phenotypic fitness analysis of an arrayed mutant collection of S. cerevisiae, we have also identified mutants of the ESCRT-III complex as being defective in peroxisome biogenesis. ESCRT-III is a cytosolic complex with diverse functions, including notably membrane scission during cytokinesis and the formation of multivesicular bodies.³⁾ Characterization of the mutants of ESCRT-III revealed defects in peroxisome biogenesis and morphology. We investigated ESCRT-III function biochemically using an in vitro PPV budding assay and showed that the addition of cytosols lacking ESCRT-III failed to release PPVs from the ER. Mutants of ESCRT-III components were also defective in forming peroxisomes in an in vivo peroxisome biogenesis assay. An exploration of the role of ATP in releasing PPVs from the ER found that PPV release is independent of ATP. We propose that ATP is required rather for the recycling of scission components, namely those of the ESCRT-III complex, during PPV formation. Finally, analysis of the ultrastructure of peroxisomes in wild-type yeast and ESCRT-III mutants by transmission electron microscopy revealed an absence of peroxisomes in ESCRT-III mutants and, instead, the presence of PPVs in contiguity with the ER. We propose that ESCRT-III functions as a positive regulator of PPV egress from the ER. This represents a novel role for ESCRT-III in regulating the formation of vesicles not only away from, but also into, the cytosol.

参考文献

1. Titorenko, V.I. and Rachubinski, R.A. (2001) The life cycle of the peroxisome. Nat. Rev. Mol. Cell Biol. 2: 357-368.
2. Mast, F.D., Jamakhandi, A. Saleem, R.A., Dilworth, D.J., Rogers, R.S., Rachubinski, R.A. and Aitchison, J.D. (2016) Peroxins Pex30 and Pex29 dynamically associate with reticulons to regulate peroxisome biogenesis from the endoplasmic reticulum. J. Biol. Chem. 291:15408-15427.
3. Henne, W.M., Stenmark, H and Emr, S.D. (2013) Molecular mechanisms of the membrane sculpting ESCRT pathway. Cold Spring Harb Perspect Biol 5:a016766.

連絡先

生体防御医学研究所 オルガネラホメオスタシス研究室
藤木 幸夫 092-642-4232 (秘書 6341)