FBS Colloquia No.205Laboratpry of Intracellular Membrace Cynamics
| Seminar or Lecture |
lysophagy: How the damaged membrane is removed & mechanistic insight of LC3-II lipidation Maho Hamasaki [Laboratory of Intracellular Membrane Dynamics] Rubicon negatively regulates osteoblast differentiation Gota Yoshida [Laboratory of Intracellular Membrane Dynamics] |
|---|---|
| Date and Time | Wednesday, January 30, 2019, 12:15-13:00 |
| Place | 2F Seminar room, BioSystems Building |
| Contact |
Maho Hamasaki |
lysophagy: How the damaged membrane is removed & mechanistic insight of LC3-II lipidation
Autophagy is induced when cells are starved and also when cells need cleaning. We will introduce the latter type of autophagy, especially lysophagy which clears damaged lysosomes. Lysosomes can be damaged by cells taken up cholesterol crystals, ureic acid crystals and other irritable particles that can be a causative of life style diseases. We will introduce our recent finding on how damaged lysosomes are removed. Also, we will introduce our recent findings on LC3 proteins and putative drug that is effective on cell cleaning type of autophagy.
Rubicon negatively regulates osteoblast differentiation
We have previously reported Rubicon negatively regulates autophagy. However, the physiological roles of Rubicon remain elusive in vivo. We now investigate the role of Rubicon in bones by generating osteoblast specific Rubicon deficient mice. We generated conditional knock out mice {Osterix-Cre/Rubicon (flox/flox)} that lack Rubicon in osteoblast. Osterix-Cre/Rubicon (flox/flox) mice progressively developed skeletal abnormalities in femur bones. In addition, Rubicon deficient osteoblast exhibited increased differentiation, mineralization and expression levels of transcription factors, such as Runx2 and Osteocalcin that are master regulators of osteoblast. Furthermore, Notch, negative regulator of osteoblast, signaling downstream transcription factors such as HeyL, Hes1 and Hes3 were expressed at lower levels in Rubicon deficient osteoblast. Consistently, we found reduction the protein expression of Notch receptor due to upregulation of autophagic flux in Rubicon deficient osteoblast. These data suggested that Notch receptor could be degraded by autophagy or reduced by other mechanisms, and now we are investigating the Notch receptor degradation mechanisms.
