NORTHWESTERN UNIVERSITY
Grant: $80,157 - National Institutes of Health - Sep. 25, 2009
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Award Description: This award is issued in response to Notice OD-09-060, Recovery Act Administrative Supplements Providing Summer Research Experiences for Students and Science Educators. DESCRIPTION (provided by applicant): Epithelial cells are polarized into distinct apical and basolateral plasma membrane domains. The apical membrane faces the outside of the body and the basolateral membrane is in contact with connective tissues. During the lifetime of any given epithelial cell it is crucial for organ function that this established polarity is maintained. For example, loss of polarity enables a cell to disintegrate from a monolayer, which is an early step in metastatic cancer. Apical and basolateral plasma membrane domains have distinct sets of lipids and plasma membrane receptors. To maintain this distinct distribution, the cells continuously need to sort newly synthesized proteins along the biosynthetic pathway and recycle internalized receptors to the correct membrane. Basolateral targeting often depends on targeting determinants in the cytoplasmic tail of a transmembrane protein and cytosolic adaptor molecules that recognize them and mediate sorting. We identified one major cytosolic component, the clathrin-adaptor complex AP-1B (Folsch et al., 1999). Clathrin adaptor complexes are tetraheteromers. Typically the medium subunit interacts directly with the sorting signals and is therefore of particular interest. The medium subunit of AP-1B, mu1B is exclusively expressed in epithelial tissues and directly interacts with basolateral cargo molecules (Folsch et al., 2001). Our work will focus on defining the molecular mechanisms of AP-1B function and its site(s) of action. Moreover, we will analyze how the membrane recruitment of AP-1B is regulated. Furthermore, we will investigate the molecular interactions leading to AP-1B mediated basolateral targeting. My laboratory will combine cell biological, biochemical and genetic approaches to resolve the following specific aims: 1) At which intracellular site(s) does AP-1B fulfill its sorting function? 2) How is AP-1B membrane recruitment and vesicle formation regulated? 3) What is the molecular basis for AP-1B specific sorting events? A better understanding of the processes by which epithelial cells maintain polarity is essential, if we want to learn which defects in molecular sorting may transform epithelial cells into cancer cells, to name only one example of diseases associated with the loss of cell polarity.
Project Description: As defined in the Award Description field
Jobs Summary: American Recovery and Reinvestment Act funds have significantly aided the research mission of Northwestern University by providing salary compensation for individuals directly involved in research, both at Northwestern and at consortium institutions, as well as at the vendor organizations who provide goods and services in support of that mission. Northwestern has employed a standard methodology for determining jobs created or retained, based on guidance presented by OMB. Jobs are reported in aggregate for the grant, comprised of calculated figures for hourly and salaried employees at Northwestern plus the reported jobs created or retained by subrecipients. The number of Northwestern hourly employees will be calculated as the number of hours charged to the grant divided by the standard hours in a full-time schedule for the period. The number of Northwestern salaried employees will be calculated based on the paid effort charged to the ARRA grant divided by the total salary. There are currently no jobs created or retained by this ARRA funded project. (Total jobs reported: 0)
Project Status: Not Started
This award's data was last updated on Sep. 25, 2009. Help expand these official descriptions using the wiki below.
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