Our goal is to understand how Golgi stacks are generated. An attractive model is that new Golgi elements arise from the COPII transport vesicles that are produced at transitional ER (tER) sites. Thus, characterizing the tER will be crucial for understanding the Golgi. For example, Golgi distribution in budding yeasts seems to be a consequence of tER distribution. In Saccharomyces cerevisiae, Golgi cisternae are dispersed throughout the cytoplasm and the entire ER functions as tER; whereas in Pichia pastoris, coherent Golgi stacks are located next to discrete tER sites. These two yeasts will be analyzed through a combination of genetics, biochemistry and microscopy to elucidate the mechanisms that define the tER-Golgi system.
Our Specific Aims are: (1) To characterize S. cerevisiae mutants defective in Golgi inheritance. This study will test the idea that Golgi inheritance is a byproduct of ER inheritance. (2) To isolate P. pastoris mutants with abnormal tER organization. Such mutants will lead us to the proteins that define tER sites, and will reveal whether Golgi distribution is indeed a consequence of tER distribution. (3) To determine how P. pastoris Sec12p is localized to tER sites. Because Sec12p is thought to be the """"""""master regulator"""""""" of the COPII assembly pathway, analyzing the localization mechanism of this protein will yield insights into tER formation. Abnormal Golgi function is a causative agent in many diseases, including cancer as well as various inherited and autoimmune diseases. Treatment of these diseases will require a cell biological understanding of the processes that establish and maintain Golgi organization. Our work aims to elucidate these basic principles of Golgi biogenesis.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM061156-04
Application #
6606974
Study Section
Cell Development and Function Integrated Review Group (CDF)
Program Officer
Shapiro, Bert I
Project Start
2000-07-01
Project End
2005-06-30
Budget Start
2003-07-01
Budget End
2004-06-30
Support Year
4
Fiscal Year
2003
Total Cost
$241,023
Indirect Cost
Name
University of Chicago
Department
Genetics
Type
Schools of Medicine
DUNS #
005421136
City
Chicago
State
IL
Country
United States
Zip Code
60637
Bhave, Madhura; Papanikou, Effrosyni; Iyer, Prasanna et al. (2014) Golgi enlargement in Arf-depleted yeast cells is due to altered dynamics of cisternal maturation. J Cell Sci 127:250-7
Glick, Benjamin S (2014) Integrated self-organization of transitional ER and early Golgi compartments. Bioessays 36:129-33
Day, Kasey J; Staehelin, L Andrew; Glick, Benjamin S (2013) A three-stage model of Golgi structure and function. Histochem Cell Biol 140:239-49
Bharucha, Nike; Liu, Yang; Papanikou, Effrosyni et al. (2013) Sec16 influences transitional ER sites by regulating rather than organizing COPII. Mol Biol Cell 24:3406-19
Montegna, Elisabeth A; Bhave, Madhura; Liu, Yang et al. (2012) Sec12 binds to Sec16 at transitional ER sites. PLoS One 7:e31156
Glick, Benjamin S; Luini, Alberto (2011) Models for Golgi traffic: a critical assessment. Cold Spring Harb Perspect Biol 3:a005215
Bhattacharyya, Dibyendu; Hammond, Adam T; Glick, Benjamin S (2010) High-quality immunofluorescence of cultured cells. Methods Mol Biol 619:403-10
Levi, Stephanie K; Bhattacharyya, Dibyendu; Strack, Rita L et al. (2010) The yeast GRASP Grh1 colocalizes with COPII and is dispensable for organizing the secretory pathway. Traffic 11:1168-79
Glick, Benjamin S; Nakano, Akihiko (2009) Membrane traffic within the Golgi apparatus. Annu Rev Cell Dev Biol 25:113-32
Papanikou, Effrosyni; Glick, Benjamin S (2009) The yeast Golgi apparatus: insights and mysteries. FEBS Lett 583:3746-51

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