COMMENTARY Granule swelling and membrane fusion in exocytosis

Cells that secrete proteins do so by a well-characterized route, the final step of which is the fusion of intracellular secretory granules with the overlying plasma membrane (Palade, 1975). This results in the exocytosis of the granule contents. Associated with this exocytosis is a swelling, of either the granules themselves or their contents. This swelling has been observed by light microscopy in the nematocysts of cnidarians (Lubbock & Amos, 1981; Holstein &Tardent, 1984), the cortical granules of the sea-urchin egg (Zimmerberg & Whitaker, 1985; Zimmerberg et al. 1985), and the mast cell granules of the beige mouse (Breckenridge & Aimers, 1987; Zimmerberg et al. 1987), and by electron microscopy in Tetrahymena and Parameaum (Satir et al. 1973; Bilinski et al. 1981), guinea-pig sperm (Yanagimachi & Usui, 1974; Green, 1978a,b, 1982), pulmonary mast cells (Caulfield et al. 1980), Limulus amoebocytes (Ornberg & Reese, 1981) and mammalian epithelial cells (Dylewski & Keenan, 1983). For the past decade or so, there have been two opposing views as to whether swelling precedes membrane fusion or follows it. The importance of knowing this sequence lies, at least in part, in the role that granule swelling may play in membrane fusion by tensioning the secretory granule membrane. A large body of experimental evidence from model experiments and a range of cell types has been interpreted as supporting the view that granule swelling precedes membrane fusion (Miller & Racker, 1976; Cohen et al. 1980; Zimmerberg et al. 1980, 1985; Akabas et al. 1984; Satir et al. 1973; Yanagimachi & Usui, 1974; Pollard et al. 1979, 1984; Caulfield et al. 1980; Hampton & Holz, 1983; Zimmerberg & Whitaker, 1985; Finkelstein et al. 1986). However, in three cell types, Paramecium, the nematocytes of the cnidarians, Rhodactis rhodostoma and Anthopleura elegantissima, and guinea-pig sperm, the evidence was held to demonstrate that fusion preceded swelling (Green, 1978a,b,c, 1982; Lubbock et al. 1981; Bilinski et al. 1981). Of the cells studied, the only one in which both views of the sequence of events have been held is guinea-pig sperm