In vivo imaging of receptor trafficking of RET in organogenesis and pathogenesis

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K21147
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General physiology; Experimental pathology
• Research Institution: Kobe University
• Principal Investigator: Ito Keisuke 神戸大学, 医学研究科, 助教 (10575468)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: RET / GDNF / Rab11 / Dynein / 細胞外基質 / Integrin / 変異型RET

Outline of Final Research Achievements

Appropriate intracellular receptor trafficking underlie normal physiological activities of cells. RET, a Glial cell line neurotrophic factor receptor plays various roles in organogenesis, but its intracellular trafficking is largely unknown. In this project, I generated a knockin mouse line that express RET-GFP fusion proteins, and analyzed intracellular trafficking of RET in living cells. I found that RET exhibited polarized trafficking pattern and this pattern largely depends on types of extracellular matrices. I also found that Rab11 and Dynein pathways regulate RET trafficking. Finally, a mutant RET that can induces multiple human diseases showed aberrant localization. Therefore, it is suggested that appropriate RET trafficking is essential for normal physiological activities, and disruption of localization pattern of mutant RET leads to pathogenesis.

Free Research Field

神経発生学