Membrane-cytoskeleton dynamics in rat parietal cells: mobilization of actin and spectrin upon stimulation of gastric acid secretion.

Abstract

Abstract. The gastric parietal (oxyntic) cell is presented as a model for studying the dynamic assembly of the skeletal infrastructure of cell membranes. A monoclonal antibody directed to a 95-kD antigen of acid-secreting membranes of rat parietal cells was characterized as a tracer of the membrane movement occurring under physiological stimuli. The membrane rearrangement was followed by immunocytochemistry both at the light and electron microscopic level on semithin and thin frozen sections from resting and stimulated rat gastric mucosa. Double labeling experiments demonstrated that a specific and massive mobilization of actin, and to a lesser extent of spectrin (fodrin), was involved in this process. In the resting state, actin and spectrin were mostly localized beneath the membranes of all cells of the gastric gland, whereas the bulk of acid-secreting membranes appeared diffusely distributed in the cytoplasmic space of parietal cells without any apparent connection with cytoskeletal proteins. In stimulated cells, both acid-secreting material and actin (or spectrin) extensively colocalized at the secretory apical surface of parietal cells, reflecting that acid-secreting membranes were now exposed at the lumen of the secretory canaliculus and that this insertion was stabilized by cortical proteins.The data are compatible with a model depicting the membrane movement occurring in parietal cells as an apically oriented insertion of activated secretory membranes from an intracellular storage pool. The observed redistribution of actin and spectrin argues for a direct control by gastric acid secretagogues of the dynamic equilibrium existing between nonassembled (or preassembled) and assembled forms of cytoskeletal proteins.

Both Microtubules and Actin Filaments Are Required for Efficient Postendocytotic Traffic of the Polymeric Immunoglobulin Receptor in Polarized Madin-Darby Canine Kidney Cells

“…Actin cytoskeletal rearrangements have been noted in gastric parietal cells in response to secretion (48). However, the relationship between these two phenomenon is unknown.…”

Segregation of Two Spectrin Isoforms: Polarized Membrane-binding Sites Direct Polarized Membrane Skeleton Assembly

“…An important future goal will be to classify other interacting membrane proteins as either inducers (that provide positional information for the membrane skeleton) or responders (that conform to membrane skeleton polarity). Many of the proteins that associate with the membrane skeleton are physiologically important factors whose position within the cell is likely to be critical to their function [e.g., sodium channels (Srinivasan et al, 1988;Rotin et al, 1994), IP3 receptor (Joseph and Samanta, 1993), H,K-ATPase (Mercier et al, 1989), and anion exchangers (Morgans and Kopito, 1993)]. Their interactions with the membrane skeleton may have evolved as a mechanism that provides access to positional information within the cell.…”

Calmodulin and calcium-dependent protease I coordinately regulate the interaction of fodrin with actin.

“…It has been hypothesized that the fodrin-based cortical cytoskeleton might serve as an organizer of topographic membrane domains, a targeting mechanism for vesicles containing membrane proteins, a stabilizer of the plasma membrane, and as a barrier to unregulated vesicle traffic (1). These processes probably involve transient changes in the plasticity of the cortical cytoskeleton and its linkage to membrane receptors and microfilaments (28). The synergistic effects of calmodulin and CDP-I on fodrin described here may be one mechanism for effecting such regulation because cycles of a-fodrin proteolysis, which allow calmodulin to rapidly and reversibly influence the fodrin skeleton, would compete with the replacement of the cleaved protein by constitutive fodrin synthesis.…”