Abstract：
:Secretion of cytolytic granules content at the immunological synapse is a highly regulated process essential for lymphocyte cytotoxicity. This process requires the rapid transfer of perforin containing lytic granules to the target cell interface, followed by their docking and fusion with the plasma membrane. Defective cytotoxicity characterizes a genetically heterogeneous condition named familial hemophagocytic lymphohistiocytosis (FHL), which can be associated with perforin deficiency. The locus of a perforin (+) FHL subtype (FHL3), observed in 10 patients, was mapped to 17q25. This region contains hMunc13-4, a member of the Munc13 family of proteins involved in vesicle priming function. HMunc13-4 mutations were shown to cause FHL3. HMunc13-4 deficiency results in defective cytolytic granule exocytosis, despite polarization of the secretory granules and docking with the plasma membrane. Expressed tagged hMunc13-4 localizes with cytotoxic granules at the immunological synapse. HMunc13-4 is therefore essential for the priming step of cytolytic granules secretion preceding vesicle membrane fusion.
journal_name
Celljournal_title
Cellauthors
Feldmann J,Callebaut I,Raposo G,Certain S,Bacq D,Dumont C,Lambert N,Ouachée-Chardin M,Chedeville G,Tamary H,Minard-Colin V,Vilmer E,Blanche S,Le Deist F,Fischer A,de Saint Basile Gdoi
10.1016/s0092-8674(03)00855-9subject
Has Abstractpub_date
2003-11-14 00:00:00pages
461-73issue
4eissn
0092-8674issn
1097-4172pii
S0092867403008559journal_volume
115pub_type
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