Evidence for M-Phase-Specific Modification of a Gap Junction Protein

Abstract

Gap junctions are intercellular junctions which permit free diffusion of ions and small molecules (up to about 1000 daltons) through proteinaceous channels connecting two adjacent cells (1). These channels are formed when hexamers of connexin (ex) proteins in each of the apposing plasma membranes become aligned, thereby creating a continuous aqueous passageway connecting the cells’ cytoplasm. This continuity of cell interiors lends itself to metabolic cooperation and has been postulated to be a principal means of maintaining tissue homeostasis (2). Aside from the proposed homeostatic function of gap junctions, these structures have been thought to play a major role in the control of cell growth and differentiation (1, 2). In fact, gap junctionmediated intercellular communication (GJIC) has been demonstrated to be regulated by a variety of growth signals, such as epidermal growth factor, tumor promoters, as well as viral and cellular src proteins (3). Moreover, the involvement of gap junctions in growth regulation is further implicated by the discovery of connexin molecules as candidate tumor suppressor proteins (4), as well as the demonstration that transfection of connexins into tumor cells reduces their tumorigenicity in vivo and/or in vitro (5,6, 7). For normal cells, cell division represents the most common and universal process in which growth controls must be exerted. Several laboratories, including ours, have reported on cell cycle-dependent GJIC using various methods, including electronmicroscopic and immunostaining analyses, Northern hybridization, dye transfer, and GAP-FRAP (4, 8, 9, 10, 11, 12). Thus, it appears that cell cycle-dependent regulation of gap junctions is a common phenomenon. Yet the molecular basis( es) for this phenomenon has not been fully elucidated. In at least one study, differential transcription was observed for cx26 and ex43 in normal human mammary epithelial cells as a function of cell cycle progression (4).