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

TL;DR

This study identifies MEA1 as a chaperone that helps assemble the AP1 complex, which is crucial for transporting cargo in cells.

Contribution

The paper introduces MEA1 as a novel bi-handed chaperone that regulates AP1 assembly through a dual-chaperone mechanism.

Findings

MEA1 stabilizes the μ1 and β1 subunits of AP1, promoting complex formation.

MEA1 and AAGAB work together to assemble the AP1 complex through a collision mechanism.

Loss of MEA1 disrupts AP1-dependent trafficking and subunit levels.

Abstract

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.

Wan et al. identify MEA1 as a chaperone that promotes assembly of the AP1 adaptor complex and is essential for cargo transport. MEA1 and AAGAB cooperate through a dual-chaperone mechanism that may be broadly applicable to protein complex assembly.

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