# Multifunctional roles of Sec13 paralogues in the euglenozoan Trypanosoma brucei

## TL;DR

This study explores the roles of two Sec13 paralogues in the parasite Trypanosoma brucei, showing they both contribute to COPII-mediated ER transport.

## Contribution

The study reveals that TbSec13.2 is involved in COPII trafficking, challenging previous assumptions about its exclusive role in the SEA/GATOR complex.

## Key findings

- Both TbSec13.1 and TbSec13.2 are essential for COPII-mediated transport of secretory cargo.
- TbSec13.2 co-localizes with TbSec24.1 at ER exit sites, indicating a functional role in COPII.
- TbSec13.2 is not restricted to the SEA/GATOR complex in trypanosomes.

## Abstract

Secretory cargos are exported from the ER via COPII-coated vesicles that have an inner matrix of Sec23/Sec24 heterotetramers and an outer cage of Sec13/Sec31 heterotetramers. In addition to COPII, Sec13 is part of the nuclear pore complex (NPC) and the regulatory SEA/GATOR complex in eukaryotes, which typically have one Sec13 orthologue. The kinetoplastid parasite Trypanosoma brucei has two paralogues: TbSec13.1, an accepted component of both COPII and the NPC, and TbSec13.2. Little is known about TbSec13.2, but others have proposed that it, and its orthologue in the distantly related diplonemid Paradiplonema papillatum, operate exclusively in the SEA/GATOR complex, and that this represents an evolutionary diversification of function unique to the euglenozoan protists. Using RNAi silencing in trypanosomes, we show both TbSec13s are essential. Knockdown of each dramatically and equally delays transport of GPI-anchored secretory cargo, indicating roles for both in COPII-mediated trafficking from the ER. Immunofluorescence and proximity labelling studies confirm that both TbSec13.1 and TbSec13.2 co-localize with TbSec24.1 to ER exit sites, and thus are functional components of the COPII machinery. Our findings indicate that TbSec13.2 function is not restricted to the SEA/GATOR complex in trypanosomes.