Modulation of GJA1 Turnover and Intercellular Communication by Proinflammatory Cytokines in the Anterior Pituitary Folliculostellate Cell Line TtT/GF

• Published in: Biology of reproduction Vol. 74; no. 1; pp. 2 - 12
• Main Authors: FORTIN, Marie-Ève, PELLETIER, R.-Marc, MEILLEUR, Mélissa-Anne, VITALE, Marfa Leiza
• Format: Journal Article
• Language: English
• Published: Madison, WI Society for the Study of Reproduction 01-01-2006
• Subjects: Animals; Biological and medical sciences; Cell Line; Cell physiology; Connexin 43 - metabolism; Fundamental and applied biological sciences. Psychology; Immunoblotting; Interleukin-1 - physiology; Mice; Microscopy, Fluorescence; Molecular and cellular biology; Paracrine Communication - physiology; Pituitary Gland, Anterior - physiology; Signal transduction; Tumor Necrosis Factor-alpha - physiology; Human; pituitary; anterior pituitary; Cytokine; Cell cell interaction; In vitro; Connexin; Signal transduction; Cell line; Tumor necrosis factor; Interleukin 1; Pituitary gland; cytokines; Localization
• ISSN: 0006-3363; 1529-7268
• DOI: 10.1095/biolreprod.105.044313

Our previous studies have advanced the idea that the folliculostellate cell GJA1 (gap junction membrane channel protein alpha1;
previously known as connexin 43)-mediated gap junctions contribute to the establishment of an intercellular network that regulates
the paracrine messages and the endocrine response within the anterior pituitary. The folliculostellate cells are targets for
growth factors and cytokines that modulate hormone secretion. Proinflammatory cytokines modulate the cell-to-cell communication
in many tissues of the body. The present study measured the effect of the proinflammatory cytokines tumor necrosis factor
and interleukin-1 on the GJA1-mediated intercellular communication, specifically the expression, localization, degradation,
and phosphorylation status of GJA1 in the folliculostellate cell line TtT/GF. The GJA1 localized to the plasma membrane and
to minute cytoplasmic vesicles in the perinuclear area. Using different antibodies that recognize distinctly the nonphosphorylated
from the phosphorylated forms of GJA1, we showed that nonphosphorylated GJA1 in Ser-368 (NP-GJA1) localized chiefly in the
cytoplasm, whereas GJA1 phosphorylated in Ser-368 (P-GJA1) localized to the plasma membrane in controls. The cytokine treatment
transiently increased 1) GJA1, NP-GJA1, and P-GJA1 levels; 2) NP-GJA1 and P-GJA1 degradation by both the lysosomal and proteasomal
pathways; and 3) cell-to-cell communication in TtT/GF cells. The results suggest that the cytokine-evoked, transient enhancement
of folliculostellate cell-mediated intercellular communication contributes to the coordination of the response among folliculostellate
cells.
Abstract
Proinflammatory cytokines increase GJA1 turnover in FS cells