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BOR - Papers in Press, published online ahead of print August 31, 2005.
Biol Reprod 2005, 10.1095/biolreprod.105.044313
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BIOLOGY OF REPRODUCTION 74, 2–12 (2006)
DOI: 10.1095/biolreprod.105.044313
© 2006 by the Society for the Study of Reproduction, Inc.


Research Article

Modulation of GJA1 Turnover and Intercellular Communication by Proinflammatory Cytokines in the Anterior Pituitary Folliculostellate Cell Line TtT/GF1

Marie-Ève Fortin, R.-Marc Pelletier, Mélissa-Anne Meilleur, and Maria Leiza Vitale 2

Department de Pathology and Cell Biology, Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada H3T 1J4

ABSTRACT

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.

anterior pituitary, cytokines, pituitary


FOOTNOTES

1 Supported by the Natural Sciences and Engineering Research Council of Canada grant OGP0194652 (to M.L.V.) and by a scholarship from Fonds de la recherche en santé du Québec to M.L.V.

2 Correspondence: Maria L. Vitale, Department of Pathology and Cell Biology, Faculty of Medicine, Université de Montréal, 2900 boulevard Edouard-Montpetit, Montréal, Québec H3T 1J4, Canada. FAX: 514 343 2459; maria.leiza.vitale{at}umontreal.ca




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Copyright © 2006 by the Society for the Study of Reproduction.