A physical mechanism of TANGO1-mediated bulky cargo export.

Ishier Raote,Vivek Malhotra,Maria F Garcia-Parajo,Marino Arroyo,Morgan Chabanon,Felix Campelo,Nikhil Walani

doi:10.7554/elife.59426

Abstract

The endoplasmic reticulum (ER)-resident protein TANGO1 assembles into a ring around ER exit sites (ERES), and links procollagens in the ER lumen to COPII machinery, tethers, and ER-Golgi intermediate compartment (ERGIC) in the cytoplasm (Raote et al., 2018). Here, we present a theoretical approach to investigate the physical mechanisms of TANGO1 ring assembly and how COPII polymerization, membrane tension, and force facilitate the formation of a transport intermediate for procollagen export. Our results indicate that a TANGO1 ring, by acting as a linactant, stabilizes the open neck of a nascent COPII bud. Elongation of such a bud into a transport intermediate commensurate with bulky procollagens is then facilitated by two complementary mechanisms: (i) by relieving membrane tension, possibly by TANGO1-mediated fusion of retrograde ERGIC membranes and (ii) by force application. Altogether, our theoretical approach identifies key biophysical events in TANGO1-driven procollagen export.

Highlights

Multicellularity requires the secretion of signaling proteins –such as neurotransmitters, cytokines, and hormones– to regulate cell-to-cell communication, and of biomechanical matrices composed primarily of proteins such as collagens, which form the extracellular matrix (ECM) (Kadler et al, 2007; Mouw et al, 2014)
To develop a theoretical model of transport intermediate formation at an ER exit sites (ERES), we extend and adapt the approach from Saleem et al, 2015 on clathrin-coated vesicle formation to include the contributions of TANGO1 proteins in modulating COPII-dependent carrier formation
This corresponds to the control case where TANGO1 is treated as an inert species that only contributes to the entropic energy

Summary

Introduction

Multicellularity requires the secretion of signaling proteins –such as neurotransmitters, cytokines, and hormones– to regulate cell-to-cell communication, and of biomechanical matrices composed primarily of proteins such as collagens, which form the extracellular matrix (ECM) (Kadler et al, 2007; Mouw et al, 2014). Like all conventionally secreted proteins, contain a signal sequence that targets their entry into the endoplasmic reticulum (ER) After their glycosylation, procollagens fold and trimerize into a characteristic triple-helical, rigid structure, which, depending on the isoform, may extend several hundred nm in length (McCaughey and Stephens, 2019). At the ERES, the formation of canonical COPII-coated carriers relies on the polymerization on the membrane surface of a largescale protein structure: the protein coat.

Results

Discussion

Conclusion