Grant: Project Grant

The Transport Protein Particle (TRAPP) complexes were first discovered in yeast. Subsequent work identified related, conserved complexes in humans. These complexes function in moving proteins between various intracellular compartments within a cell. Although they share a core of common proteins, there are unique proteins that are associated with the core to form the various complexes (three complexes in yeast, two in higher eukaryotes). While the functions of the complexes in yeast are better understood, the functions of the mammalian complexes are less clear. In addition, several of the subunits that associate with the complex in humans have been shown to have functions independent of the complex. Furthermore, recent work has led to the identification of individuals that have mutations in TRAPP proteins. Curiously, these individuals all have different phenotypes depending on which TRAPP protein is mutated. Thus, understanding the functions of the mammalian TRAPP proteins and their role in disease is a necessary next step in our understanding of these complexes. This present application seeks to understand the functions of two specific subunits called C11 and C2L. In order to facilitate this work, we are developing a simplified in vitro assay that reconstitutes transport in the secretory pathway. We will use wild type TRAPP complexes as well as complexes harboring mutations in the aforementioned proteins to assess their ability to reconstitute membrane traffic in this pathway. The results of these studies will provide insight into specific human disorders that are linked to TRAPP mutations and will allow clinicians to more quickly assess new disorders that may be linked to these complexes.