Plasma cell immunoglobulin secretion. Arrest is accompanied by alterations the golgi complex

Abstract

Conditions influencing Ig secretion by plasma cells have been studied with suspensions of murine plasma cells and myeloma cells by determining the release of (3)H-Ig after a pulse of biosynthetic labeling with L- [4,5-(3)H]-leucine. Ig secretion is insensitive to a variety of hormones, mediators, cyclic nucleotide derivatives, extracellular calcium depletion, and agents acting on mierotubules or microfilaments; i.e., to a number of factors which are involved in the regulation of secretion by cells with a storage compartment. On the other hand, Ig secretion is markedly inhibited by conditions which (a) lower intracellular calcium levels (ionophore A 23187 in Ca(++)-free medium), (b) induce partial sodium/potassium equilibration (the ionophores monensin and nigericin and, in the case of myeloma cells, ouabain and incubation in K(+)-free medium) or (c) uncouple oxidative phosphorylation. The first two situations are accompanied by striking alterations of the ultrastructural appearance of the Golgi complex, different in each case. These ultrastructural observations, together with autoradiographic experiments after a short pulse with L-[4,5-(3)H]-leucine, have led to the following hypothesis: (a) under Ca(++) depletion (3)H-Ig passes to Golgi vesicles but these vesicles are incapable of fusion or migration and therefore accumulate in exaggerated numbers in the Golgi area; (b) under partial Na(+)/K(+) equilibration, (3)H-Ig passes to Golgi vesicles which have an exaggerated tendency to fuse with other Golgi elements, thereby generating large vacuoles which store increasing amounts of Ig; (c) under energy block, multiple membrane fission and fusion events are inhibited and there is therefore, little intracellular transport of (3)H-Ig or alteration of cell ultrastructure.

Sorting and endocytosis of viral glycoproteins in transfected polarized epithelial cells.

“…In principle, the accumulation of G protein in cytoplasmic vesicles may result from interiorization of surface molecules, or from impaired delivery to the cell surface of G molecules synthesized during the chloroquine treatment (45). These possibilities were examined in transfected cultures that re-ceived the protein synthesis inhibitor cycloheximide belbre (45 min) the addition of chloroquine, and were incubated for several hours in the presence of both drugs.…”

Modulation of glycosylation and transport of viral membrane glycoproteins by a sodium ionophore.

“…As a result of viral inhibition of host protein synthesis, only one or a few viral membrane glycoproteins are synthesized in infected cells. These viruses possess limited genetic capacity, and the glycosylation and transport of their membrane glycoproteins to the cell surface are probably carried out by the same systems used by the host cell for biogenesis of its own membrane glycoproteins.Monovalent ionophores such as monensin, which is reported to interfere with the translocation of secretory as well as most membrane glycoproteins, have been used to characterize the pathways of intracellular glycoprotein transport in eucaryotic cells (18,(37)(38)(39)(40)(41)43). In addition, the effects of monensin on IgM and H2 glycosylation in lymphoid cells and fibronectin glycosylation in cultured human fibroblasts, as well as its influence on oligosaccharide maturation of…”

Undersulfated β‐D‐xyloside glycosaminoglycans are secreted in the presence of the ionophore monensin

“…Monovalent ionophores such as monensin have served as useful probes for studying this process since they disrupt the intracellular flow without permanently damaging cells and they also have minimal effects upon energy production [ 13] and protein synthesis [4]. Monensin does cause substantial changes in cellular ultrastructure, affecting primarily mitochondrial and Golgi architecture [1,6]. Although fibroblasts are also affected in this way [6], we have found that, in the chondrocytes used here, both the Golgi elements and rough endoplasmic reticuhim are altered by the presence of monensin (unpublished).…”