Retromer articles from across Nature Portfolio

Polarity-deficient epithelial cells are eliminated through Sas-Ptp10D-mediated suppression of EGFR signalling during cell competition. Here the authors show the constitutively active, phosphomimetic WASH can activate both EGFR and Hippo signalling and thereby, induces the overgrowth of these polarity-deficient cells in Drosophila and in proliferating epithelial cells, WASH activation differentially affects the separate recycling routes of EGFR and its inhibitor Ptp10D.

OTULIN is a linear ubiquitin hydrolase that regulates ubiquitin homeostasis. Here the authors identify the adaptor of the endosomal retromer complex sorting nexin 27 (SNX27) as a binding partner of OTULIN and determine the structure of the OTULIN-SNX27 complex, which reveals a secondary interface through which OTULIN non-catalytically antagonizes SNX27 retromer assembly and cargo loading.

Though ubiquitin is known to broadly influence endosomal trafficking, few ubiquitin-utilizing enzymes targeting endosomal regulators are known. Here, the authors find that the deubiquitylating enzyme (DUB) USP32 influences endosomal membrane dynamics by deubiquitinating Rab7.

The retromer complex (the vacuolar protein sorting heterotrimer Vps26–Vps29–Vps35) has been resolved in association with membranes and the sorting nexin protein Vps5 using cryo-electron tomography.

Recycling from endosomes to the plasma membrane is an important step in cell homeostasis. The retromer/SNX27/WASH complex recycles numerous receptors, but key ones are still unaccounted for. Now a related conserved heterotrimer, called retriever, has been identified that, together with SNX17, the CCC complex and WASH, mediates the recycling of α₅β₁ integrins.

Parathyroid hormone analog PTH(1–34), used clinically to treat osteoporosis, forms a stable complex with its receptor and prolongs cAMP production even after internalization and recruitment to endosomes. New data suggest this signaling cascade is stimulated by β-arrestins and terminated by retromer.