A trapper keeper for TRAPP, its structures and functions

Abstract

During biosynthesis many membrane and secreted proteins are transported from the endoplasmic reticulum, through the Golgi and on to the plasma membrane in small transport vesicles. These transport vesicles have to undergo budding, movement, tethering, docking, and fusion at each organelle of the biosynthetic pathway. The transport protein particle (TRAPP) complex was initially identified as the tethering factor for endoplasmic reticulum (ER)-derived COPII vesicles, but the functions of TRAPP may extend to other areas of biology. Three forms of TRAPP complexes have been discovered to date, and recent advances in research have provided new insights on the structures and functions of TRAPP. Here we provide a comprehensive review of the recent findings in TRAPP biology.

Fig. 1

TRAPP complexes function in various membrane trafficking pathways. TRAPPI tethers COPII vesicles at ERGIC but its role in this part of the vesicular transport may start at the ER exit sites. TRAPPII mediates intra-Golgi traffic, Golgi exit, endosome-to-Golgi traffic, and the trafficking of autophagy proteins Atg8 and Atg9 from Golgi to PAS. TRAPPIII has function in anterograde transport at the Golgi and also regulates autophagy. For each of the functions of TRAPP (numbered in the figure), supporting evidence is listed as follows: 1. TRAPPC3/Bet3 interacts with Sec23. Many TRAPP subunits are localized in the ERGIC. TRAPPI acts as GEF for Rab1/Ypt1 at ERGIC. RNAi depletion or yeast genetic studies showed blocks in early transport [2, 17, 20, 21, 24, 26, 39]. 2. TRAPPC9 and TRAPPC10 interact with COPI coat subunit and possible retrograde vesicular transport. Yeast genetic studies on the TRAPPII-specific subunits showed defects in intra-Golgi transport. TRAPPII serves as GEF for Ypt31/32 and plays a critical role in mediating the traffic exiting the Golgi toward the plasma membrane in yeast [2, 9, 17, 53, 85]. 3. RNAi depletion of TRAPPIII-specific subunit, TRAPPC8, blocked transport at the Golgi. Trs85 mutation slightly impaired anterograde transport at the Golgi [20, 40]. 4. Yeast Trs120 mutants showed defect in endosome to Golgi traffic [77]. 5. TRAPPIII-specific subunit Trs85 is required for the localization of Ypt1 to PAS. RNAi depletion of TRAPPC8 demonstrated this subunit (possibly mammalian TRAPPIII) negatively regulates autophagy. TRAPPIII subunits physically interact with other proteins in the autophagic protein network [7, 22]. 6. Mutations of yeast TRAPPII-specific subunit Trs130 impaired the transport of Atg8 and Atg9 to PAS [40]. EE Early endosome, LE late endosome, PAS pre-autophagosomal structure, IM isolation membrane, PM plasma membrane, ER endoplasmic reticulum, ERGIC ER-Golgi intermediate compartment

Fig. 2

Structure of TRAPP complexes. Three forms of TRAPP complexes have been revealed from structural studies of the yeast complexes. The structures of mammalian complexes are more preliminary, particularly TRAPPII and TRAPPIII. In both systems, additional proteins have been assigned to TRAPPII or TRAPPIII but not presented in the drawings because the evidence is still preliminary

Fig. 3

Hypothetic model of how TRAPP tethers COPII vesicles. a TRAPPI binds to COPII vesicle via Bet3/TRAPPC3 and Sec23 interaction. The interaction is mediated either by Bet3B away from where Ypt1/Rab1 binds, or by Bet3A on the same side of Ypt1/Rab1 interaction. b When COPII vesicle approaching the target membrane, Ypt1/Rab1 exchange is catalyzed by TRAPPI. c (a) Ypt1/Rab1-GTP interacts with tethering mediator Uso1/p115. (b1) Uso1/p115 brings COPII vesicle to close proximity to the target membrane. Partial uncoating of COPII vesicle and SNARE pair occur to facilitate fusion. (b2-d) TRAPPI is released from COPII vesicle and TRAPPII-specific subunits are assembled onto TRAPPI to become TRAPPII. The complex dimerizes; and (e) performs downstream TRAPPII specific functions