Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2003-11-18
pubmed:databankReference
pubmed:abstractText
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.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0092-8674
pubmed:author
pubmed:issnType
Print
pubmed:day
14
pubmed:volume
115
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
461-73
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:14622600-Amino Acid Sequence, pubmed-meshheading:14622600-Base Sequence, pubmed-meshheading:14622600-Cell Degranulation, pubmed-meshheading:14622600-Cell Polarity, pubmed-meshheading:14622600-Cells, Cultured, pubmed-meshheading:14622600-Chromosome Mapping, pubmed-meshheading:14622600-Cloning, Molecular, pubmed-meshheading:14622600-DNA Mutational Analysis, pubmed-meshheading:14622600-Exocytosis, pubmed-meshheading:14622600-Female, pubmed-meshheading:14622600-Gene Expression Profiling, pubmed-meshheading:14622600-Genetic Complementation Test, pubmed-meshheading:14622600-Histiocytosis, Non-Langerhans-Cell, pubmed-meshheading:14622600-Humans, pubmed-meshheading:14622600-Male, pubmed-meshheading:14622600-Membrane Fusion, pubmed-meshheading:14622600-Molecular Sequence Data, pubmed-meshheading:14622600-Mutation, pubmed-meshheading:14622600-Organ Specificity, pubmed-meshheading:14622600-Pedigree, pubmed-meshheading:14622600-Protein Conformation, pubmed-meshheading:14622600-Proteins, pubmed-meshheading:14622600-RNA, Messenger, pubmed-meshheading:14622600-Secretory Vesicles, pubmed-meshheading:14622600-T-Lymphocytes, Cytotoxic
pubmed:year
2003
pubmed:articleTitle
Munc13-4 is essential for cytolytic granules fusion and is mutated in a form of familial hemophagocytic lymphohistiocytosis (FHL3).
pubmed:affiliation
INSERM U429, Hôpital Necker-Enfants Malades, 75743 Paris, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't