TRAPP Complexes in Secretion and Autophagy

Abstract

TRAPP is a highly conserved modular multi-subunit protein complex. Originally identified as a “transport protein particle” with a role in endoplasmic reticulum-to-Golgi transport, its multiple subunits and their conservation from yeast to humans were characterized in the late 1990s. TRAPP attracted attention when it was shown to act as a Ypt/Rab GTPase nucleotide exchanger, GEF, in the 2000s. Currently, three TRAPP complexes are known in yeast, I, II, and III, and they regulate two different intracellular trafficking pathways: secretion and autophagy. Core TRAPP contains four small subunits that self assemble to a stable complex, which has a GEF activity on Ypt1. Another small subunit, Trs20/Sedlin, is an adaptor required for the association of core TRAPP with larger subunits to form TRAPP II and TRAPP III. Whereas the molecular structure of the core TRAPP complex is resolved, the architecture of the larger TRAPP complexes, including their existence as dimers and multimers, is less clear. In addition to its Ypt/Rab GEF activity, and thereby an indirect role in vesicle tethering through Ypt/Rabs, a direct role for TRAPP as a vesicle tether has been suggested. This idea is based on TRAPP interactions with vesicle coat components. While much of the basic information about TRAPP complexes comes from yeast, mutations in TRAPP subunits were connected to human disease. In this review we will summarize new information about TRAPP complexes, highlight new insights about their function and discuss current controversies and future perspectives.

Bi-allelic mutations in TRAPPC2L result in a neurodevelopmental disorder and have an impact on RAB11 in fibroblasts

“…These complexes, found in yeast and higher eukaryotes, are involved in endoplasmic reticulum (ER)-to-Golgi and endosome-to-Golgi trafficking, and autophagy 11 17–23. The human TRAPP complexes are referred to as TRAPP II and III 24. These complexes are composed of a common core of subunits that include TRAPPC1, TRAPPC2, TRAPPC2L, TRAPPC3, TRAPPC4, TRAPPC5 and TRAPPC6, but are distinguished by the association of complex-specific proteins; TRAPPC9 and TRAPPC10 in TRAPP II, and TRAPPC8, TRAPPC11, TRAPPC12 and TRAPPC13 in TRAPP III 25.…”

Chaperoning SNARE assembly and disassembly

“…2a). The known MTCs can be divided into three families, each conserved from yeast to mammals: the homotypic fusion and vacuolar protein sorting (HOPS) family 54,55 , the complexes associated with tethering containing helical rods (CATCHR) family 10,56 , and the transport protein particle (TRAPP) family 57 . The HOPS and CATCHR families, although structurally unrelated, are particularly notable for their large number of direct interactions with other proteins that are implicated in vesicle docking and fusion, such as vesicle coat proteins, Rab GTPases, SNAREs and SM proteins (TABLE 1).…”

Breaking fat: The regulation and mechanisms of lipophagy

“…TRAPP-II is then able to activate Rab18, promoting its subsequent recruitment to the LD to regulate lipolysis [51]. TRAPP complexes are known to be involved in the autophagic process [52]; therefore, future investigations will be useful in determining whether Rab18-TRAPP interactions play any defined role in the selective process of lipophagy. Other Rabs, such as Rab25, have recently been suggested to participate in the autophagic turnover of retinyl ester-enriched LDs from hepatic stellate cells (HSCs) [53].…”