TY - JOUR T1 - ADAP’s intrinsically disordered region is an actin sponge regulating T cell motility JF - bioRxiv DO - 10.1101/2021.12.14.472590 SP - 2021.12.14.472590 AU - Nirdosh Dadwal AU - Janine Degen AU - Jana Sticht AU - Tarek Hilal AU - Tatjana Wegner AU - Peter Reichardt AU - Ruth Lyck AU - Michael Abadier AU - Miroslav Hons AU - Charlie Mix AU - Benno Kuropka AU - Heike Stephanowitz AU - Fan Liu AU - Burkhart Schraven AU - Christoph Wülfing AU - Stefanie Kliche AU - Christian Freund Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/12/14/2021.12.14.472590.abstract N2 - Intrinsically disordered proteins (IDPs) play a vital role in biological processes that rely on transient molecular compartmentation1. In T cells, the dynamic switching between migration and adhesion mandates a high degree of plasticity in the interplay of adhesion and signaling molecules with the actin cytoskeleton2,3. Here, we show that the N-terminal intrinsically disordered region (IDR) of adhesion- and degranulation-promoting adapter protein (ADAP) acts as a multipronged scaffold for G- and F-actin, thereby promoting actin polymerization and bundling. Positively charged motifs, along a sequence of at least 200 amino acids, interact with both longitudinal sides of G-actin in a promiscuous manner. These polymorphic interactions with ADAP become constrained to one side once F-actin is formed. Actin polymerization by ADAP acts in synergy with a capping protein but competes with cofilin. In T cells, ablation of ADAP impairs adhesion and migration with a time-dependent reduction of the F-actin content in response to chemokine or T cell receptor (TCR) engagement. Our data suggest that IDR-assisted molecular crowding of actin above the critical concentration defines a new mechanism to regulate cytoskeletal dynamics. The principle of IDRs serving as molecular sponges to facilitate regulated self-assembly of filament-forming proteins might be a general phenomenon.Competing Interest StatementThe authors have declared no competing interest. ER -