title: Growth arrest induces primary-cilium formation and sensitizes IGF-1-receptor signaling during differentiation induction of 3T3-L1 preadipocytes.
abstract: The first stage of 3T3-L1 adipocyte differentiation is growth arrest, which is achieved by contact inhibition at confluence. In growth-arrested confluent 3T3-L1 preadipocytes, alpha-tubulin acetylation and primary-cilium formation were induced. The blockade of primary-cilium formation by suppressing IFT88 or Kif3a inhibited 3T3-L1 adipocyte differentiation. IGF-1 (IGF-I)-receptor signaling, which is essential for differentiation induction, was sensitized by the formation of a primary cilium in confluent 3T3-L1 preadipocytes. The receptor located in primary cilium was more sensitive to insulin stimulation than that not located in cilia. During cilium formation, insulin receptor substrate 1 (IRS-1), one of the important downstream signaling molecules of the IGF-1 receptor, was recruited to the basal body at which it was phosphorylated on tyrosine by the receptor kinase in cilia. Akt-1, an important signal molecule of the IGF-1 receptor in adipocyte differentiation, was also activated at the basal body. These IGF-1-receptor signaling processes were all inhibited in IFT88- or Kif3a-knockdown cells. Thus, the primary cilium and its basal body formed an organized signaling pathway for the IGF-1 receptor to induce adipocyte differentiation in confluent 3T3-L1 preadipocytes.
authors: State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors: Di
authors: D
authors: Zhu
authors: Shuo
authors: S
authors: Shi
authors: Hongzhong
authors: H
authors: Wang
authors: Kan
authors: K
authors: Liao
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D002923:Cilia / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D016547:Kinesins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C490202:Kif3a protein, mouse; D034741:RNA, Small Interfering; C490898:Tg737Rpw protein, mouse; D025521:Tumor Suppressor Proteins; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D051057:Proto-Oncogene Proteins c-akt; D016547:Kinesins