Maemoto Yuki, Maruyama Tomohiro, Nemoto Kazuaki, Baba Takashi, Motohashi Manae, Ito Akihiro, Tagaya Mitsuo, Tani Katsuko
School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji, Japan.
Department of Biological Informatics and Experimental Therapeutics, Graduate School of Medicine and Faculty of Medicine, Akita University, Akita, Japan.
Front Cell Dev Biol. 2020 Jul 23;8:670. doi: 10.3389/fcell.2020.00670. eCollection 2020.
DDHD1 and DDHD2 are both intracellular phospholipases A and hydrolyze phosphatidic acid . Given that phosphatidic acid participates in neurite outgrowth, we examined whether DDHD1 and DDHD2 regulate neurite outgrowth. Depletion of DDHD1 from SH-SY5Y and PC12 cells caused elongation of neurites, whereas DDHD2 depletion prevented neurite elongation. Rescue experiments demonstrated that the enzymatic activity of DDHD1 is necessary for the prevention of neurite elongation. Depletion of DDHD1 caused enlargement of early endosomes and stimulated tubulation of recycling endosomes positive for phosphatidic acid-binding proteins syndapin2 and MICAL-L1. Knockout of DDHD1 enhanced transferrin recycling from recycling endosomes to the cell surface. Our results suggest that DDHD1 negatively controls the formation of a local phosphatidic acid-rich domain in recycling endosomes that serves as a membrane source for neurite outgrowth.
DDHD1和DDHD2均为细胞内磷脂酶A，可水解磷脂酸。鉴于磷脂酸参与神经突生长，我们研究了DDHD1和DDHD2是否调节神经突生长。从SH-SY5Y和PC12细胞中耗尽DDHD1会导致神经突伸长，而耗尽DDHD2则会阻止神经突伸长。拯救实验表明，DDHD1的酶活性对于防止神经突伸长是必要的。耗尽DDHD1会导致早期内体增大，并刺激对磷脂酸结合蛋白syndapin2和MICAL-L1呈阳性的回收内体形成微管。敲除DDHD1可增强转铁蛋白从回收内体向细胞表面的循环。我们的结果表明，DDHD1负向控制回收内体中局部富含磷脂酸结构域的形成，该结构域作为神经突生长的膜来源。
