Lysosomal membrane protein LAPTM4a functions in multiple drug resistance.

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K19010
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General medical chemistry
• Research Institution: Kyushu University
• Principal Investigator: Hirota Yuko 九州大学, 薬学研究院, 助教 (50588259)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: リソソーム / エンドソーム / 多剤耐性

Outline of Final Research Achievements

Lysosomal-associated protein transmembrane 4α (LAPTM4α) interacts with E3 ubiquitin ligase Nedd4-1 via its PY motifs, and as well as with Eps15 via its DIII domain. LAPTM4α is trafficked from trans-Golgi network (TGN) to lysosomes in dependent of Nedd4-1’s interaction but not of its ubiquitination, and is sequestered within multi vesicular bodies (MVBs) and degraded into lysosomes. Interestingly, these steps are independent of the endosomal sorting complexes required for transport (ESCRT) machinery. The ESCRT protein expression interference prevented the recruitment of LAPTM4α onto the MVBs, which implies that the ESCRT complex proteins might contribute to the sorting of LAPTM4α from TGN to the endosomes but not to its sequestering within MVBs. Furthermore, the overexpression of LAPTM4α in mammmalian cells exposed to anticarcinogenic agent resulted in the increase of cell viability significantly, implying that LAPTM4α might function in drug resistance.

Free Research Field

細胞生物学