Single molecule analysis of the regulatory mechanism of LFA-1-dependent adhesion longevity

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K21524
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Immunology; Functional biochemistry
• Research Institution: Kansai Medical University
• Principal Investigator: KONDO Naoyuki 関西医科大学, 医学部, 助教 (30570840)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: 一分子解析 / LFA-1 / Rap1 / Kindlin-3 / 免疫シナプス / ICAM-1 / 全反射顕微鏡 / 平面脂質二重膜

Outline of Final Research Achievements

In order to elucidate the spatiotemporal regulatory mechanism of LFA-1 on immunological synapse (IS), a supramolecular structure formed during adaptive immune response, we established single molecule measurement system of LFA-1/ICAM-1 binding events and investigated its regulatory mechanism.
We found that distribution of LFA-1 binding time is heterogeneous: long-term binding events occur only at a region where LFA-1 activatory factors such as Rap1 and Kindlin-3 localize. Furthermore, Rap1/Kindlin-3 deficient cells showed reduced number of long-term binding events, resulting in the defect in cell adhesion.
Collectively, we propose that the regulation of LFA-1 function is attributed to spatial allocation of cellular factors, which control binding time of LFA-1/ICAM-1.

Free Research Field

タンパク質科学, 一分子生物学, 免疫学, 細胞生物学