Chen, Baoyu
Mayo Clinic
Roy J. Carver Department of Biochemistry, Biophysics & Molecular Biology, Iowa State University, 2437 Pammel Drive, Ames, IA 50011, USA.
Citations 2
Structural Organization of the Retriever-CCC Endosomal Recycling Complex
Boesch, Daniel J. , Singla, Amika , Han, Yan , Kramer, Daniel A. , Liu, Qi , Suzuki, Kohei , Long, Xin, Medlyn, Michael, Billadeau, Daniel D. , Chen, Baoyu , Medlyn, Michael J. , Chen, Zhe , Chen, Baoyu , Burstein, Ezra , Liu, Qi , Juneja, Puneet , Zhao, Xuefeng , Long, Xin, Burstein, Ezra
No container title available | June 16, 2023 | Volume: No volume available | Issue: No issue available | Pages: No page available
Abstract The recycling of membrane proteins from endosomes to the cell surface is vital for cell signaling and survival. Retriever, a trimeric complex of VPS35L, VPS26C and VPS29, together with the CCC complex comprising CCDC22, CCDC93, and COMMD proteins, plays a crucial role in this process. The precise mechanisms underlying Retriever assembly and its interaction with CCC have remained elusive. Here, we present the first high-resolution structure of Retriever determined using cryogenic electron microscopy. The structure reveals a unique assembly mechanism, distinguishing it from its remotely related paralog, Retromer. By combining AlphaFold predictions and biochemical, cellular, and proteomic analyses, we further elucidate the structural organization of the entire Retriever-CCC complex and uncover how cancer-associated mutations disrupt complex formation and impair membrane protein homeostasis. These findings provide a fundamental framework for understanding the biological and pathological implications associated with Retriever-CCC-mediated endosomal recycling.
Arf GTPase activates the WAVE regulatory complex through a distinct binding site
Yang, Sheng , Tang, Yubo , Liu, Yijun , Brown, Abbigale J., Schaks, Matthias , Ding, Bojian , Kramer, Daniel A. , Miętkowska, Magdalena, Alekhina, Olga , Billadeau, Daniel D. , Wang, Junmei , Chen, Baoyu , Alekhina, Olga , Billadeau, Daniel D , Chowdhury, Saikat , Wang, Junmei , Rottner, Klemens , Chen, Baoyu , Li, Ding
Science Advances | December 14, 2022 | Volume: 8 | Issue: 50 | Pages: No page available
Cross-talk between Rho- and Arf-family guanosine triphosphatases (GTPases) plays an important role in linking the actin cytoskeleton to membrane protrusions, organelle morphology, and vesicle trafficking. The central actin regulator, WAVE regulatory complex (WRC), integrates Rac1 (a Rho-family GTPase) and Arf signaling to promote Arp2/3-mediated actin polymerization in many processes, but how WRC senses Arf signaling is unknown. Here, we have reconstituted a direct interaction between Arf and WRC. This interaction is greatly enhanced by Rac1 binding to the D site of WRC. Arf1 binds to a previously unidentified, conserved surface on the Sra1 subunit of WRC, which, in turn, drives WRC activation using a mechanism distinct from that of Rac1. Mutating the Arf binding site abolishes Arf1-WRC interaction, disrupts Arf1-mediated WRC activation, and impairs lamellipodia formation and cell migration. This work uncovers a new mechanism underlying WRC activation and provides a mechanistic foundation for studying how WRC-mediated actin polymerization links Arf and Rac signaling in cells.