Molecular function(s) of MOT48 in the dynein pre-assembly

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K15117
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cell biology
• Research Institution: Osaka University
• Principal Investigator: Yamamoto Ryosuke 大阪大学, 理学研究科, 助教 (10743114)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: 繊毛 / 前集合 / pre-assembly / MOT48 / TWI1 / PF13 / ダイニン / Chlamydomonas

Outline of Final Research Achievements

Motility of cilia is driven by the gigantic motor-protein complexes called "ciliary dyneins". Ciliary dyneins are folded/assembled from their subunits (HC/IC/LC) in the cytoplasm, and this process is called "pre-assembly". Defects in the dynein pre-assembly cause various severe human diseases, but the underlying molecular mechanism(s) of the dynein pre-assembly has been poorly understood. In this study, by analyzing several pre-assembly deficient mutants of a green alga (Chlamydomonas reinhardtii) we aimed to elucidate the molecular mechanism(s) of the dynein pre-assembly. We identified ciliary dynein species, which were folded/assembled by the three Chlamydomonas pre-assembly factors (PF13/MOT48/TWI1). Further, we found that the functions of these three dynein pre-assembly factors were somewhat redundant and complementary, suggesting the mechanism of dynein pre-assembly is far more complex than has been previously thought.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

繊毛ダイニンの細胞質内における組み立て/折り畳み(前集合)異常は、左右軸逆位/気管支炎/不妊等を含む重篤な人体疾患の引き金となる。しかしながら、その重要性にも関わらず、繊毛ダイニン前集合機構の分子基盤には不明な点が多い。我々は、2本の運動性繊毛を持つ単細胞緑藻クラミドモナスの変異株を用いて、遺伝学的/生化学的/構造生物学的な手法により前集合の分子基盤の一端の解明に努めた。その結果、2種の新規前集合異常株(mot48-2及びtwi1株)の単離に成功し、複数種の繊毛ダイニン前集合因子(PF13/MOT48/TWI1)が具体的にどの繊毛ダイニン種の組み立て/折り畳みに関与するのかを明らかにした。