Munc13-4/rab27a complex in NK cell and CTL function
Thursday 22 January 2009
Dr. Peter van der Sluijs / Drs Edo Elstak
Project
Mutations in RAB27a cause Griscelli syndrome type II (GS2). The disease is characterized by haemophagocytosis, and the inability of cytotoxic T cells and Natural Killer cells to release their lytic granule contents and kill target cells. We identified Munc13-4 as a partner of rab27a and showed that the two proteins function in the granule exocytosis pathway. Interestingly enough, others found that mutations in MUNC13-4 cause Familal Haemophagocytic Lymfohistiocytosis type 3 (FHL3) with symptoms that are related to, but distinct from those in GS2. In this project we propose to define the signaling pathways that lead from T cell receptor activation to rab27a and to characterize the function of the Munc13-4/rab27a complex in NK cells and CTLs.
Techniques
Molecular biology methods, proteomics, fluorescence techniques including live cell imaging and FACS analysis.
Duration
6 or 9 months
Contact
Dr. Peter van der Sluijs, p.vandersluijs@umcutrecht.nl, tel. 088 75 575 78
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