The HOPS Tethering Complex is Required to Maintain Signaling Endosome Identity and TORC1 Activity

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 2022 Apr 11

PMID 35404387

Authors

Jieqiong Gao

Raffaele Nicastro

Marie-Pierre Peli-Gulli

Sophie Grziwa

Zilei Chen

Rainer Kurre

Jacob Piehler

Claudio De Virgilio

Florian Frohlich

Christian Ungermann

Affiliations

Soon will be listed here.

Abstract

The endomembrane system of eukaryotic cells is essential for cellular homeostasis during growth and proliferation. Previous work showed that a central regulator of growth, namely the target of rapamycin complex 1 (TORC1), binds both membranes of vacuoles and signaling endosomes (SEs) that are distinct from multivesicular bodies (MVBs). Interestingly, the endosomal TORC1, which binds membranes in part via the EGO complex, critically defines vacuole integrity. Here, we demonstrate that SEs form at a branch point of the biosynthetic and endocytic pathways toward the vacuole and depend on MVB biogenesis. Importantly, function of the HOPS tethering complex is essential to maintain the identity of SEs and proper endosomal and vacuolar TORC1 activities. In HOPS mutants, the EGO complex redistributed to the Golgi, which resulted in a partial mislocalization of TORC1. Our study uncovers that SE function requires a functional HOPS complex and MVBs, suggesting a tight link between trafficking and signaling along the endolysosomal pathway.

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