Proteolysis in neuronal axons and its impairment

2015 Fiscal Year Final Research Report

• Project Area: Brain Environment
• Project/Area Number: 23111004
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Juntendo University
• Principal Investigator: Uchiyama Yasuo 順天堂大学, 医学部, 教授 (10049091)
• Co-Investigator(Renkei-kenkyūsha): Koike Masato 順天堂大学, 大学院医学研究科, 教授 (80347210) ; Sunabori Takehiko 順天堂大学, 大学院医学研究科, 助教 (00407115) ; Sasaki Mitsuho 順天堂大学, 大学院医学研究科, 助教 (20432536) ; Suzuki Chigure 順天堂大学, 大学院医学研究科, 助教 (40536629)
• Project Period (FY): 2011-04-01 – 2016-03-31
• Keywords: オートファジー / リソソーム / 軸索 / カテプシンD / Atg9 / p62 / NBR1 / 選択的オートファジー

Outline of Final Research Achievements

We examined the quality control in neuronal axons through proteolysis and its impairment, and found that p62 and NBR1 was localized only in somatodendrites but not in axons and their terminals of neurons. N-terminal regions of p62 and NBR1 were responsible for this polarized localization. The intraneuronal target components of p62 and NBR1 in CD-deficient neurons were dysfunctional lysosomes whose surface membrane was decorated by p62/NBR1, together with ubiquitin. As for Atg9A-deficient brains, the KO mice did not live beyond four weeks of age. p62 and NBR1, together with ubiquitin, accumulated in neuronal cell bodies at postnatal day (P) 15, but these accumulations were decreased at P28. Severe degenerative changes proceeded only in axons and their terminals at P28. Atg9A-deficiency induced dysgenesis of the corpus callosum and anterior commissures, while the axonal extensions of primary cultured neurons from the mouse embryos were significantly impaired in primary neurons.

Free Research Field

神経生物学