USP32 regulates late endosomal transport and recycling through deubiquitylation of Rab7

• DOI: 10.1038/s41467-019-09437-x
• Publication Date: 2019-03-29T11:03:19Z
• Authors: Aysegul Sapmaz; Ilana Berlin; Erik Bos; Ruud H. Wijdeven; Hans Janssen; Rebecca Konietzny; Jimmy J. Akkermans; Ayse E. Erson-Bensan; Roman I. Koning; Benedikt M. Kessler; Jacques Neefjes; Huib Ovaa
• Keywords: Small GTPase; Deubiquitinating enzyme; Retromer

Abstract The endosomal system is a highly dynamic multifunctional organelle, whose complexity regulated in part by reversible ubiquitylation. Despite the wide-ranging influence of ubiquitin processes, relatively few enzymes utilizing have been described to control endosome integrity and function. Here we reveal deubiquitylating enzyme (DUB) ubiquitin-specific protease 32 (USP32) as powerful player this context. Loss USP32 inhibits late (LE) transport recycling LE cargos, resulting dispersion swelling compartment. Using SILAC-based ubiquitome profiling identify small GTPase Rab7—the logistical centerpiece biology—as substrate USP32. Mechanistic studies that effector RILP prefers ubiquitylation-deficient Rab7, while retromer-mediated benefits from an intact cycle Rab7 Collectively, our observations suggest ubiquitylation helps switch between its various functions, thereby maintaining global spatiotemporal order system.