Proper distribution of proteins and organelles is an essential property of eukaryotic cells. This """"""""polarity"""""""" allows them to undergo processes like division, polarized growth, and differentiation. One way you can establish polarity is by directing membrane traffick. This regulation is a conserved process from yeast to mammals, so the basic principles of how that is occurring can be uncovered in yeast and then studied in more detail in animal models. I propose to study the role of phosphatidylinositol-4-phosphate (PI4P) in secretion, specifically, to evaluate its role in Myo2p activity. Myo2p is the motor protein responsible for the movement and segregation of several cellular components during the cell cycle. One of its cargoes is the secretory vesicles, that originate from the Golgi. Abundant evidence indicate that PI4P is the major PI species in the Golgi, plus we have preliminary genetic and imaging data suggesting that PI4P may play a role in Myo2p-dependent secretory vesicle transport. I plan to investigate this further by various genetic techniques, namely overexpression suppression analysis, generation and characterization of mutants,etc. Also, using modified versions of the yeast two-hybrid and conventional biochemical assays, I will try to identify the elusive secretory vesicle Myo2-receptor. My results, together with others in the lab and elsewhere, will help our understanding of how Myo2p is regulated, which is essential for the cell's survival.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31GM077098-05
Application #
7790621
Study Section
Special Emphasis Panel (ZRG1-GGG-G (29))
Program Officer
Gaillard, Shawn R
Project Start
2006-04-01
Project End
2011-03-31
Budget Start
2010-04-01
Budget End
2011-03-31
Support Year
5
Fiscal Year
2010
Total Cost
$38,460
Indirect Cost
Name
Cornell University
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
872612445
City
Ithaca
State
NY
Country
United States
Zip Code
14850
Santiago-Tirado, Felipe H; Legesse-Miller, Aster; Schott, Daniel et al. (2011) PI4P and Rab inputs collaborate in myosin-V-dependent transport of secretory compartments in yeast. Dev Cell 20:47-59
Santiago-Tirado, Felipe H; Bretscher, Anthony (2011) Membrane-trafficking sorting hubs: cooperation between PI4P and small GTPases at the trans-Golgi network. Trends Cell Biol 21:515-25