Defects in membrane trafficking can lead to numerous diseases including: neurodegenerative disorders, kidney and vascular disease, and cancer. Rab GTPases are small proteins that play critical roles in membrane trafficking events including: membrane transport, tethering, and vesicle fusion. To function properly, Rabs must continually cycle between active and inactive states through interactions with guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs), respectively. Although much is known about how Rabs function in membrane trafficking, relatively few Rabs have had their GEFs identified. Recently, we have identified a novel protein complex called the SCD complex. This complex contains a differentially expressed in normal and neoplastic cells (DENN) domain and binds RabE1 in a nucleotide dependent manner consistent with GEF function. RabE1 is most closely related to mammalian Rab8, which recently has been implicated in the development of human carcinoma and remains a potential gene target for chemotherapy. It is the goal of this proposal to understand the role of the SCD complex in RabE1 mediated vesicle trafficking. This work will provide insight into how multi-subunit GEF complexes regulate Rab GTPases, and may have implications in understanding how Rabs and their regulatory proteins function in human disease.

Public Health Relevance

The improper regulation of Rab GTPases can lead to numerous diseases including: neurodegenerative disorders, kidney and vascular disease, and cancer. Recently, we have identified the SCD complex, a novel protein complex that binds RabE1 in a nucleotide dependent manner and contains domains consistent with a role in regulating RabE1. It is the goal of this proposal to understand the role of the SCD complex in RabE1 mediated vesicle trafficking.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32GM112446-01A1
Application #
8909207
Study Section
Special Emphasis Panel (ZRG1-F05-D (21))
Program Officer
Sakalian, Michael
Project Start
2015-04-01
Project End
2017-03-31
Budget Start
2015-04-01
Budget End
2016-03-31
Support Year
1
Fiscal Year
2015
Total Cost
$54,194
Indirect Cost
Name
University of Wisconsin Madison
Department
Biochemistry
Type
Schools of Earth Sciences/Natur
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Mayers, Jonathan Russell; Hu, Tianwei; Wang, Chao et al. (2017) SCD1 and SCD2 Form a Complex That Functions with the Exocyst and RabE1 in Exocytosis and Cytokinesis. Plant Cell 29:2610-2625