TANGO1 assembles into rings around COPII coats at ER exit sites

Abstract

TANGO1 interacts with COPII components to generate a transport carrier for export of large cargo from the endoplasmic reticulum. Raote et al. show that TANGO1 molecules assemble to form a closed ribbon structure that encircles COPII components.

A physical mechanism of TANGO1-mediated bulky cargo export

“…izes with proteins of the TANGO1 family (such as TANGO1 itself, the TANGO1-like protein 59 cTAGE5, and the spliced isoform TANGO1-Short) (Saito et al, 2011;Maeda, Saito and 60 Katada, 2016; Raote et al, 2018). Recently, we visualized procollagen export domains with 61 high lateral spatial resolution using stimulated emission depletion (STED) nanoscopy in mam-62 malian tissue cultured cells (Raote et al, 2017. These studies revealed that TANGO1 63 organizes at the ERES into ring-like structures, of ~200 nm in diameter, that corral COPII com-64 ponents.…”

“…CCC = 0 or if ̅ 3 = 1/ (Figure 2A). Computation of the preferred size of TANGO1 rings 304 TANGO1 rings surround COPII components (Raote et al, 2017), corresponding to a filament 305 full wetting condition (that is, = 1), as presented in Figure 1B (analysis of the ERES size in 306 dewetting conditions is presented in the Supplementary Information). Under wetting condi-307 tions, a ring of radius Z[\j is formed by a TANGO1 filament wrapping around a COPII patch.…”

“…In this situation, the neck of the growing carrier 389 prematurely closes without being able to fully incorporate long semi-rigid procollagen mole-390 cules, which are not efficiently recruited to the COPII export sites due to the lack of TANGO1 391 ( Figure 3A). In our model for TANGO1 ring formation, we proposed that one of the potential 392 roles of such a ring is to act as a linactant to stabilize free COPII subunits at the edge of the 393 polymerized structure (Glick, 2017;Raote et al, 2017) and hence prevent or kinetically delay 394 the premature closure of the bud neck ( Figure 3B). Moreover, mechanical forces pointing to-395 wards the cytosolic side of the bud, either from the ER lumen (e.g.…”

Epidermal aspects of type VII collagen: Implications for dystrophic epidermolysis bullosa and epidermolysis bullosa acquisita

“…38 Heat shock protein 47, a chaperon that specifically binds to collagens, has also been identified as a guiding molecule of collagens to COPII vesicles by interacting with the SH3 domain of TANGO1. 39,40 ER Golgi intermediate compartment (ERGIC) membranes are recruited by soluble N-ethylmaleimide-sensitive factor activating protein receptor (SNARE) proteins to COL7 carrier vesicles at the ER exit site, and fusion of ERGIC with ER membranes builds a mega carrier that contains very large molecules, 41,42 such as COL7 (which may reach 467 nm in length). 43 Despite these major advancements in COL7 physiology, there remain unsolved questions that have not yet been explored.…”

Membrane Transport at an Organelle Interface in the Early Secretory Pathway: Take Your Coat Off and Stay a While

“…The Tango1/cTage5 family of proteins has also been implicated in the formation of “specialized” transport carriers, which can accommodate large cargoes, including collagens that are ≈300 nm in length. Fairly elaborate mechanisms have been proposed to describe how Tango1/cTage5 complexes may facilitate this action, based on the premise that the inner COPII coat exists in two distinct complexes after assembly on ER membranes, bound either to Tango1/cTage5 or Sec13‐Sec31 . However, direct evidence for this is lacking, and localization studies consistently show the presence of both Tango1/cTage5 and Sec13‐Sec31 at all ER subdomains harboring Sec23‐Sec24 .…”