The elongation of primary cilia via the acetylation of α-tubulin by the treatment with lithium chloride in human fibroblast KD cells.
Primary cilium, an organelle found on nearly every cell in the human body, typically serves as the mechanical sensor of the cell. Lithium ion is known to promote the elongation of primary cilia in a variety of cell types, but it is unknown whether lithium is involved in the acetylation of α-tubulin which is essential for the assembly of primary cilia. In order to reveal the relationship between the elongation of primary cilia with lithium and the acetylation of α-tubulin, we first observed the formation and structure of primary cilia in KD cells, a cell line deriving fibroblasts in human labium. Subsequently, by immunohistochemical and western blot analysis we elucidated that the length of primary cilia and acetylation of α-tubulin are regulated by lithium chloride (LiCl) in the medium in a time- and concentration-dependent manner. We next performed the RT-PCR, RNAi-based experiments and biochemical study using an inhibitor of glycogen synthase kinase-3βGSK-3β). We found that LiCl mobilizes the α-tubulin N-acetyltransferase 1 (αTAT1) in the signaling pathway mediating GSK-3β and adenylate cyclase III. In conclusion, our results suggested that LiCl treatments activate αTAT1 by the inhibition of GSK-3β and promote the α-tubulin acetylation, and then elongate the primary cilia.
Department of Anatomy, Graduate School of Medicine, Teikyo University, 2-11-1 Kaga Itabashi-Ku, Tokyo, 173-8605, Japan, nakakura@med.teikyo-u.ac.jp.
Takashi
T
Nakakura
Anshin
A
Asano-Hoshino
Takeshi
T
Suzuki
Kenjiro
K
Arisawa
Hideyuki
H
Tanaka
Yoshihisa
Y
Sekino
Yoshiko
Y
Kiuchi
Kazuhiro
K
Kawai
Haruo
H
Hagiwara
D000107:Acetylation / Q000187:drug effects; D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000378:metabolism; D015153:Blotting, Western; D002460:Cell Line; D002923:Cilia / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D018021:Lithium Chloride / Q000494:pharmacology*; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D010766:Phosphorylation / Q000187:drug effects; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014404:Tubulin / Q000378:metabolism*
D014404:Tubulin; D000123:Acetyltransferases; C049182:alpha-tubulin acetylase; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; D000262:Adenylyl Cyclases; C421784:adenylate cyclase 3; D018021:Lithium Chloride