SNAREs and Epithelial Cell Polarity

Additional research in the Weimbs Lab is focused on investigating the role of SNAREs in membrane trafficking, epithelial cell polarity and the life cycle of viruses.

Membrane Trafficking and Cell Polarity: The majority of human cell types are polarized, i.e. they exhibit asymmetry, which is essential to their function. This includes epithelial cells that form barriers between the outside world and the underlying basement membrane and connective tissue. Epithelial cells are the functional units of most major human organs such as the kidney, liver, lungs, gastrointestinal tract, exocrine glands etc. The function of epithelial cells depends on their ability to form two distinct surfaces: the apical and basolateral plasma membrane domains which differ in their protein composition and function. Establishment and maintenance of this so-called "cell polarity" depends on the precise targeting of proteins to the apical and basolateral plasma membrane domains using vesicular transport pathways. Understanding the mechanisms that underlie polarized trafficking is of fundamental importance to understand function and dysfunction of polarized cells. Newly synthesized plasma membrane proteins are sorted inside epithelial cells and are specifically targeted to either the apical or basolateral surface by vesicular transport. We are particularly interested in the mechanism of membrane fusion between a transport vesicle and its target membrane. Membrane fusion involves the so-called "SNARE" machinery which consists of specific proteins on the vesicle membrane (v-SNAREs) and on the target membrane (t-SNAREs). The Weimbs Laboratory has found that two SNAREs of the syntaxin family, syntaxin 3 and 4, specifically function in trafficking to the apical and basolateral plasma membrane, respectively. Current research is aimed at investigating novel signaling functions of these SNARE proteins.

The life cycle of viruses: The Weimbs Lab is also researching how viruses affect SNARE proteins to their advantage to support their replication. We have previously shown how human cytomegalovirus (HCMV) uses SNARE proteins to produce virions. We are also studying the Picornaviridae family of positive-strand RNA viruses. We are probeing the relationship between pathogen and host proteins, and how viral protein interactions with host proteins can increase the efficacy of such a compact viral genome.