Immune system, genetics and regulation / edited by Eli E. Sercarz, Leonard A. Herzenberg, C. Fred Fox.

  • ICN-UCLA Symposium on the Immune System (1977 : Park City, Utah)
Date:
1977
Catalogue details

Licence: Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)

Credit: Immune system, genetics and regulation / edited by Eli E. Sercarz, Leonard A. Herzenberg, C. Fred Fox. Source: Wellcome Collection.

    700/792 (page 676)
    676 82. MARTIN С. RAFF AND DURWAIШ LAWSON channel closing, which appears to occur within minutes of opening, is also unknown. 2^ Since the introduction of Ca into the cells by means of the ionophore A23187 gives results that are morphologically indistinguishable from those seen when mast cells are stimu¬ lated by cross-linking ligands, it is likely that, in each case, it is an influx of Ca^* that initiates the sequence of events that leads to membrane fusion and exocytosis. How Ca^* acts inside the cell in this respect is unknown; since Mg^* cannot substitute for Ca^^ (9) and since ATP is required following Ca^* influx (21) , it is probable that the mechanism is more complex than simple charge neutralisation or lipid segregation, which may explain the role of Ca^* in the fusion of negatively charged liposomes (35). The fact that degranu- lation is localised when stimulated by Con A on Sepharose 4B beads (see above) indicates that Ca2+ acts locally to initiate membrane fusion, rather than activating a process which is transmitted to the whole cell. Although it is difficult to determine from static pictures the sequence of events in a rapidly evolving process such as exocytosis in mast cells, we feel that our observations are most consistent with the following hypothetical sequence of events (29) : the influx of Ca^^ leads to a multifocal dis¬ placement of cytoplasmic components and proteins in plasma and underlying granule membranes (possibly mediated by contractile elements, such as microfilaments) which allows the two membranes to fuse; the fused lipid bilayers, being depleted of protein and thus, perhaps, unstable, bulge from the cell to form a bleb which vesiculates and breaks off, opening the granule contents to the extracellular space so that histamine is released by cation exchange. In this way, membrane lipid is lost (and thus cell size remains unchanged) and the membrane proteins are conserved and possibly re-used in forming new granule membranes. It seems likely that at least some of these postulated events occur in other examples of exocytosis and that membrane protein displacement is a common feature of transient membrane fusion. REFERENCES 1. Gilula, N.B. (1974) IniCeZZ Cormuniaatïon R.P. Cox, ed. John Wiley and Sons, Inc., New York, p.l. 2. Gorski, J. and Gannon, F. (1976) A Rev. Physiol. 38,425. 3. Ellner, J.J., Lypsky, P.E. and Rosenthal, A.S. (1976) J. Immunol. 116,868. 4. Rosenstreich, D.L., Farrar, J.J. and Dougherty, S. (1976) J. Immunol. 116,131. 5. Habu, S. and Raff, M.C. (1977) (submitted for publication). M