期刊
JOURNAL OF CELL SCIENCE
卷 126, 期 11, 页码 2424-2435出版社
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/jcs.117846
关键词
Rab35; Centaurin-beta 2; ACAP2; Arf6; MICAL-L1; EHD1; Endocytic recycling; Neurite outgrowth
类别
资金
- Ministry of Education, Culture, Sports, and Technology of Japan [24370077, 24657125]
- Daiichi-Sankyo Foundation of Life Science
- Japan Society for the Promotion of Science
- International Advanced Research and Education Organization of Tohoku University
- Grants-in-Aid for Scientific Research [24657125] Funding Source: KAKEN
Endocytic recycling is a process in which molecules that have been internalized are recycled back to the plasma membrane, and although it is crucial for regulating various cellular events, the molecular nexus underlying this process remains poorly understood. Here we report a molecular link between two gatekeepers for endocytic recycling, the molecular switch Rab35 and the molecular scissors EHD1, that is mediated by two distinct Rab35 effectors during neurite outgrowth of PC12 cells. Rab35 forms a tripartite complex with MICAL-L1 and centaurin-beta 2/ACAP2 and recruits them to perinuclear Arf6-positive endosomes in response to nerve growth factor stimulation. MICAL-L1 and centaurin-beta 2 then cooperatively recruit EHD1 to the same compartment by functioning as a scaffold for EHD1 and as an inactivator of Arf6, respectively. We propose that Rab35 regulates the formation of an EHD1-association site on Arf6-positive endosomes by integrating the functions of two distinct Rab35 effectors for successful neurite outgrowth.
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