Although it is well documented that intact microtubules are required for various steps of membrane traffic, the molecular mechanism of how microtubules participate in the transport of cargo between subcellular organelles and to the plasma membrane is still incomplete. Much of the work in the field has focused on microtubule motor-mediated vesicle transport, but little is known about other, non-microtubule motor molecules that might regulated localized microtubular dynamics of couple membrane traffic to the microtubule network. The main purpose of our research is the study of the molecular mechanisms coupling membrane traffic to the cellular cytoskeleton. We have previously identified a protein of 22.3 kDa predicted molecular mass, named p22, which belongs to the EF-hand super-family of calcium-binding proteins. We have shown that p22 is required for membrane traffic and in our preliminary data, we show that p22 associates with microtubules in vivo and in vitro. Interestingly, the p22 staining pattern appears punctate along the microtubules consistent with it being associated with regions of vesicular movement along the microtubules. Based on it structural homology to signal transducers as calcineurin and calmodulin, our current model for the function of p22 is that p22 acts to modulate membrane traffic by transducing calcium signals to downstream effectors. These in turn could be involved in regulating the attachment of membranes to microtubules, in modulating localized microtubule dynamics or in controlling microtubular motor activity. The research outlined in this application will allow us to reveal the role this novel protein plays in membrane traffic. Significantly, p22 is one of the first identified non- motor proteins that is likely to regulate membrane traffic through its association with the cellular cytoskeleton. The functional characterization of p22 will be important to the understanding of cellular processes like cell migration and cell polarity as well as of abnormal processes like tumor cell response to both growth inhibitors and stimulators, which have been shown to be mediated by dynamic and complex interactions between cytoskeletal rearrangements and membrane traffic.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM057519-02
Application #
2910416
Study Section
Cellular Biology and Physiology Subcommittee 1 (CBY)
Project Start
1998-05-01
Project End
2003-04-30
Budget Start
1999-05-01
Budget End
2000-04-30
Support Year
2
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Virginia
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
001910777
City
Charlottesville
State
VA
Country
United States
Zip Code
22904