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<p>Bidirectional trafficking between the <i>trans</i>-Golgi network (TGN) and endolysosomal compartments lies at the intersection of biosynthetic and degradative pathways. At the center of this trafficking route is the adaptor protein complex 1 (AP1), a heterotetramer essential for cargo recognition and vesicle budding. Here, we identified Male-Enhanced Antigen 1 (MEA1), a previously uncharacterized protein, as a critical AP1 regulator. Loss of MEA1 resulted in depletion of AP1 subunits and impaired trafficking of AP1-dependent cargoes. Mechanistically, MEA1 acts as a bi-handed chaperone, simultaneously engaging and stabilizing the μ1 and β1 subunits of AP1. The MEA1-stabilized μ1 and β1 collide with the γ and σ1 subunits stabilized by Alpha- and Gamma-Adaptin Binding Protein (AAGAB), another bi-handed chaperone, leading to formation of the tetrameric AP1 adaptor and release of both chaperones. These findings identify MEA1 as a key AP1 regulator and uncover a dual chaperone collision mechanism potentially generalizable to multiprotein complex assembly.</p>

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Regulation of AP1 adaptor assembly by the bi-handed chaperone MEA1

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年1月20日

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  • Chun Wan,
  • Jingyi Wu,
  • Yan Ouyang,
  • Harrison Puscher,
  • Yuan Tian,
  • Suzhao Li,
  • Qian Yin,
  • Jingshi Shen

摘要

Bidirectional trafficking between the trans-Golgi network (TGN) and endolysosomal compartments lies at the intersection of biosynthetic and degradative pathways. At the center of this trafficking route is the adaptor protein complex 1 (AP1), a heterotetramer essential for cargo recognition and vesicle budding. Here, we identified Male-Enhanced Antigen 1 (MEA1), a previously uncharacterized protein, as a critical AP1 regulator. Loss of MEA1 resulted in depletion of AP1 subunits and impaired trafficking of AP1-dependent cargoes. Mechanistically, MEA1 acts as a bi-handed chaperone, simultaneously engaging and stabilizing the μ1 and β1 subunits of AP1. The MEA1-stabilized μ1 and β1 collide with the γ and σ1 subunits stabilized by Alpha- and Gamma-Adaptin Binding Protein (AAGAB), another bi-handed chaperone, leading to formation of the tetrameric AP1 adaptor and release of both chaperones. These findings identify MEA1 as a key AP1 regulator and uncover a dual chaperone collision mechanism potentially generalizable to multiprotein complex assembly.