Analysis of SCAMP1 function in secretory vesicle exocytosis by means of gene targeting in mice

Secretory carrier membrane proteins (SCAMPs) comprise a family of ubiquitou s membrane proteins of transport vesicles with no known function. Their uni versal presence in all cells suggests a fundamental role in membrane traffi c, SCAMPs are particularly highly expressed in organelles that undergo regu lated exocytosis, such as synaptic vesicles and mast cell granules. Of the three currently known SCAMPs, SCAMPI is the most abundant. To investigate t he possible functions of SCAMPI, we generated mice that lack SCAMP1, SCAMP1 -deficient mice are viable and fertile. They exhibit no changes in the over all architecture or the protein composition of the brain or alterations in peripheral organs. Capacitance measurements in mast cells demonstrated that exocytosis could be triggered reliably by GTP gamma S in SCAMP1-deficient cells. The initial overall capacitance of mast cells was similar between wi ld type and mutant mice, but the final cell capacitance after completion of exocytosis, was significantly smaller in SCAMP1-deficient cells than in wi ld type cells, Furthermore, there was an increased proportion of reversible fusion events, which may have caused the decrease in the overall capacitan ce change observed after exocytosis, Our data show that SCAMP1 is not essen tial for exocytosis, as such, and does not determine the stability or size of secretory vesicles, but is required for the full execution of stable exo cytosis in mast cells, This phenotype could be the result of a function of SCAMP1 in the formation of stable fusion pores during exocytosis or of a ro le of SCAMPI in the regulation of endocytosis after formation of fusion por es.