CIN85 and CD2AP Are Novel Constituents of Dynamic Tubular Recycling Endosomes That Regulate Recycling Upon Recruitment by MICAL-L1.

Recycling endosomes are essential for membrane trafficking, retrieving internalized cell surface receptors and lipids to the plasma membrane. In this study, we investigate the dynamics of tubular recycling endosomes (TREs) and their regulation. We demonstrate that TREs are highly dynamic structures that first undergo biogenesis and later fission upon internalization of CD98, a known clathrin-independent cargo. Our findings identify two new constituents and novel regulators of TRE function, CD2AP and CIN85, which are recruited to TRE through interactions with MICAL-L1 via their SH3 domains. Depletion of either CD2AP or CIN85 impairs recycling, demonstrating that these proteins play important roles in TRE function. Our study highlights the importance of coordinated protein interactions in maintaining endosomal function and identifies CD2AP and CIN85 as key regulators of the recycling pathway, potentially through their impact on the actin cytoskeleton. Understanding these mechanisms provides new insights into membrane trafficking and may have implications for diseases where endosomal recycling is disrupted.