|
Courses:
Cell and Molecular Biology (BIO 214), Scientific Perspectives (GSCI
104).
Research Interests: Protein Traffic in Polarized
Epithelial Cells
Collectively, the cells of the human body make
about 20 thousand different proteins. These proteins play a variety of
roles in
maintaining homeostasis including cell to cell communication,
metabolism, cell structure and nutrient transport. Crucial to the
function of new proteins is that they are transported to the correct
location in or outside of the cell in which they are made. For example,
proteins that communicate directly between adjacent cells must be
directed to the cell membrane, while proteins that play a role in
transport of nutrients through the blood must be secreted from the cell
into the circulation. The process by which proteins move from one
destination to another within a cell is termed “protein traffic”
Because of the vast number of proteins constantly being produced and
moving through the cell, protein traffic is a carefully orchestrated
process involving targeting signals present on the protein,
“sign-posts” throughout the cell helping to guide the protein and
final recognition mechanisms to insure proper delivery.
For membrane proteins, this process is particularly interesting in
polarized epithelial cells (PECs). The membrane of PECs is divided into
two distinct membrane domains, each made up of a different population
of membrane proteins. Therefore, traffic of of membrane proteins must
be highly specific in these cells. Misdirection to the opposite
membrane domain can result in loss of cell polarity leading to loss of
cell function, and disease.
I am interested in the mechanisms by which membrane proteins are
directed to their final destination in PECs. We have found that
proteins with different targeting signals take different routes to the
cell membrane in PECs despite starting at the same place and eventually
reaching the same membrane domain. We postulate that the
different cellular compartments encountered on these routes may play a
role in differentially guiding the protein to the cell membrane;
however, the reasons for this are unclear. Because PECs line the
surfaces of all of our organs, there are numerous cell models that
allow us to study protein traffic including those of the kidney, lung
and intestine. These studies can be done by traditional
biochemical methods as well as confocal microscopy, which allows us to
visualize both fixed locations of proteins and real-time movement of
proteins throughout the cell.
Selected
Publications:
Cresawn KO, Potter BA, Oztan A, Guerriero CJ,
Ihrke G, Goldenring JR, Apodaca G, Weisz OA. 2007. Differential
involvement of endocytic compartments in the biosynthetic traffic of
apical proteins. EMBO J. 26: 3737-48.
Ellis MA, Potter BA, Cresawn KO, Weisz OA. 2006. Polarized biosynthetic
traffic in renal epithelial cells: sorting, sorting, everywhere.
Am J Physiol Renal Physiol. 291: F707-13.
Cresawn KO, Fraites TJ, Wasserfall C, Atkinson M, Lewis M, Porvasnik S,
Liu C, Mah C, Byrne BJ. 2005. Impact of humoral immune response
on distribution and efficacy of recombinant adeno-associated
virus-derived acid alpha-glucosidase in a model of glycogen storage
disease type II. Hum Gene Ther. 16: 68-80.
|
|
