Investigation of Rab35 and EPI64C continue to be important to our research objectives, given our finding that EPI64C and Rab35 regulate a recycling pathway in T-cells and contribute to IS formation, most likely by participating in TCR transport to the immunological synapse. Because of the singular usefulness of knockout mice in understanding key biological functions of gene, we have been expending much of our effort in this direction. Therefore, we have created conditional knockout mice for EPI64C and Rab35. Breeding of EPI64C knockout mice indicate that even a conventional EPI64C knockout has apparently normal immune system development. Testing of T-cell functions in vitro, including conjugate formation, is underway to determine whether there are selective defectives not evident in the intact mouse. Breeding of Rab35 knockout mice reveals that the conventional knockout is embryonic lethal. Therefore crossing to lck-Cre and CD19-Cre mice is underway to assess lineage specific defects within the immune system. Collaboratively, we demonstrated that recycling of the Ca2+-activated K+ channel, KCa2.3, is dependent upon Rab35/EPI64C.Roles of other molecules in T-cell recognition are being analyzed in their respective projects, ERM in BC 010995, and Myo1G in BC 010993.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC009257-37
Application #
8552612
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
37
Fiscal Year
2012
Total Cost
$41,783
Indirect Cost
Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
Gao, Yajuan; Balut, Corina M; Bailey, Mark A et al. (2010) Recycling of the Ca2+-activated K+ channel, KCa2.3, is dependent upon RME-1, Rab35/EPI64C, and an N-terminal domain. J Biol Chem 285:17938-53
Sobocinski, Gregg P; Toy, Katherine; Bobrowski, Walter F et al. (2010) Ultrastructural localization of extracellular matrix proteins of the lymph node cortex: evidence supporting the reticular network as a pathway for lymphocyte migration. BMC Immunol 11:42
Patino-Lopez, Genaro; Dong, Xiaoyun; Ben-Aissa, Khadija et al. (2008) Rab35 and its GAP EPI64C in T cells regulate receptor recycling and immunological synapse formation. J Biol Chem 283:18323-30