モリタ　マサユキ   Masayuki Morita   森田　将之    所属   川崎医科大学  医学部 基礎医学　解剖学    職種   講師
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	The Lipid-Binding Defective Dynamin 2 Mutant in Charcot-Marie-Tooth Disease Impairs Proper Actin Bundling and Actin Organization in Glomerular Podocytes.
掲載誌名	正式名：Frontiers in cell and developmental biology 略　 称：Front Cell Dev Biol ISSNコード：2296634X/2296634X
掲載区分	国外
巻・号・頁	10
著者・共著者	Eriko Hamasaki, Natsuki Wakita, Hiroki Yasuoka, Hikaru Nagaoka, Masayuki Morita, Eizo Takashima, Takayuki Uchihashi, Tetsuya Takeda, Tadashi Abe, Ji-Won Lee, Tadahiro Iimura, Moin A Saleem, Naohisa Ogo, Akira Asai, Akihiro Narita, Kohji Takei, Hiroshi Yamada
発行年月	2022
概要	Dynamin is an endocytic protein that functions in vesicle formation by scission of invaginated membranes. Dynamin maintains the structure of foot processes in glomerular podocytes by directly and indirectly interacting with actin filaments. However, molecular mechanisms underlying dynamin-mediated actin regulation are largely unknown. Here, biochemical and cell biological experiments were conducted to uncover how dynamin modulates interactions between membranes and actin in human podocytes. Actin-bundling, membrane tubulating, and GTPase activities of dynamin were examined in vitro using recombinant dynamin 2-wild-type (WT) or dynamin 2-K562E, which is a mutant found in Charcot-Marie-Tooth patients. Dynamin 2-WT and dynamin 2-K562E led to the formation of prominent actin bundles with constant diameters. Whereas liposomes incubated with dynamin 2-WT resulted in tubule formation, dynamin 2-K562E reduced tubulation. Actin filaments and liposomes stimulated dynamin 2-WT GTPase activity by 6- and 20-fold, respectively. Actin-filaments, but not liposomes, stimulated dynamin 2-K562E GTPase activity by 4-fold. Self-assembly-dependent GTPase activity of dynamin 2-K562E was reduced to one-third compared to that of dynamin 2-WT. Incubation of liposomes and actin with dynamin 2-WT led to the formation of thick actin bundles, which often bound to liposomes. The interaction between lipid membranes and actin bundles by dynamin 2-K562E was lower than that by dynamin 2-WT. Dynamin 2-WT partially colocalized with stress fibers and actin bundles based on double immunofluorescence of human podocytes. Dynamin 2-K562E expression resulted in decreased stress fiber density and the formation of aberrant actin clusters. Dynamin 2-K562E colocalized with α-actinin-4 in aberrant actin clusters. Reformation of stress fibers after cytochalasin D-induced actin depolymerization and washout was less effective in dynamin 2-K562E-expressing cells than that in dynamin 2-WT. Bis-T-23, a dynamin self-ass
DOI	10.3389/fcell.2022.884509
PMID	35620056