Ferro-Novick Lab
Welcome to the Ferro-Novick Lab!
 
The goal of our research program is to understand how the specificity of vesicle traffic is maintained and how organelles are inherited from mother to daughter cells.
 
Vesicle Traffic and Autophagy
 
We are determining how organelles maintain their identity amidst a constant flow of membrane traffic.  Focusing on traffic between the ER and Golgi complex in both yeast and mammalian cells, we have described several key sequential interactions that are needed to define the direction of membrane flow. Using mutants that disrupt vesicle traffic between the ER and Golgi we have identified novel protein complexes, like the TRAPPI complex (described below) and a casein kinase, as key players in these trafficking events. In vitro transport assays are being used to define how these players interact with each other to ensure that a transport vesicle will only fuse once it reaches its correct target membrane.
 
Ras-like GTPases (called Rabs) interact in signal cascades that regulate the flow of membrane traffic. Rabs are molecular switches that are active in their GTP-bound form and inactive when bound to GDP. The TRAPP complexes (TRAPPI, TRAPPII and TRAPPIII) are multimeric guanine nucleotide exchange factors (GEF) that activate the GTPase Rab1 (Ypt1p in yeast). These complexes share several subunits that are required for its GEF activity. How each of the shared subunits contributes to this activity has recently been defined. The smaller TRAPP complex, TRAPPI, specifically binds to ER-derived vesicles and marks them for fusion with the Golgi. The larger complex, TRAPPII, is a Rab1 GEF that contains adaptor subunits that target it to the Golgi to mediate Golgi traffic.
 
Recently, a third TRAPP complex (TRAPPIII) has been implicated in autophagy, a catabolic process that targets the degradation of proteins and organelles for lysosomal degradation. Understanding the mechanism of autophagy is important for the study of cancer and certain neurological diseases.  The TRAPPIII complex contains the core TRAPP subunits that are required for GEF activity and a unique adaptor subunit that targets it to a preautophagosomal compartment (called the PAS) where it mediates autophagy.  The role that TRAPPIII and Rab1/Ypt1p plays in autophagy is currently being investigated.

ER Structure and Inheritance

The objective of these studies is to define how the ER gets its shape and the process by which it is delivered from mother to daughter cells. To achieve this goal, a genetic approach has been used to identify the machinery that structures the ER and moves it into daughter cells. This approach has led to the identification of a track and motor that moves ER tubules into daughter cells, a putative receptor for cortical ER in daughter cells, and proteins that structure the ER. Orthologues of these conserved components have been implicated in neurological disorders.
 
A more detailed description of our research can be found here.