Cdc42 defect reveals insights into microvilli organization and function in T cell immunity

• 成果类型: Article
• 署名作者: Soh, Won-Chang; Park, Sang-Moo; Park, Jeong-Su; Karabulut, Hatice; Kang, Hee-Tae; Kang, Sun-Kyoung; Kim, Min-Sang; Park, Jihwan; Lee, Sunjae; Kim, Hye-Ran; Jun, Chang-Duk
• 署名单位: Gwangju Institute of Science & Technology (GIST); Gwangju Institute of Science & Technology (GIST); National Cancer Center - Korea (NCC)
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-10320
• DOI: 10.1073/pnas.2505291122
• 发表日期: 2025-07-29
• 关键词: negative selection; positive selection; receptor; tcr; molecules; thymus; rho

摘要

Microvilli on T cells differ from those on epithelial cells, exhibiting filopodia-like characteristics that facilitate the clustering of molecules essential for sensing and cell migration. Recently, they have also been recognized as the structures from which T cell immunological synaptosomes (TIS) are released. In this study, we examined a key determinant of microvilli organization during T cell development and explored the functional roles of these structures, particularly in relation to T cell behaviors. During thymocyte maturation, single-positive thymocytes were found to develop more and longer microvilli than double-positive thymocytes. However, the deletion or inhibition of Cdc42, a small Rho family protein, significantly reduced both the number and length of microvilli in single-positive thymocytes, leading to decreased cell mass. This reduction in microvilli correlates with a decrease in antigen recognition, leading to diminished T cell activation and adhesion, as well as reduced TIS production, while intrinsic migratory properties remain unaffected. These findings highlight the filopodia-like characteristics of T cell microvilli. In this context, Cdc42 contributes significantly to microvilli formation, thereby shaping T cell function.