|
|
|
|
|
|
|
|
|||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | |||||
First published online 26 June 2003
doi: 10.1242/jcs.00631
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Research Article |
1 Department of Biological Sciences, Purdue University, West Lafayette, IN
47907-1392, USA
2 Departments of Paediatrics and Physiology and Pharmacology, Child Health
Research Institute, University of Western Ontario, London, Ontario N6C 2V5,
Canada
* Author for correspondence (e-mail: sfk{at}bilbo.bio.purdue.edu)
Accepted 23 April 2003
Gap junctions are intercellular channels that provide direct passage of small molecules between adjacent cells. In pancreatic acini, the connexin26 (Cx26) and connexin32 (Cx32) proteins form functional channels that coordinate the secretion of digestive enzymes. Although the function of Cx26/Cx32 gap junctions are well characterized, the regulatory circuits that control the spatial and temporal expression patterns of these connexin genes are not known. In an effort to identify the molecular pathways that regulate connexin gene expression, we examined Cx26 and Cx32 gene activities in mice lacking the basic helix-loop-helix transcription factor Mist1 (Mist1KO). Mist1, Cx26 and Cx32 are co-expressed in most exocrine cell types, and acinar cells from Mist1KO mice exhibit a highly disorganized cellular architecture and an altered pattern of expression for several genes involved in regulated exocytosis. Analysis of Mist1KO mice revealed a dramatic decrease in both connexin proteins, albeit through different molecular mechanisms. Cx32 gene transcription was greatly reduced in all Mist1KO exocrine cells, while Cx26 gene expression remained unaffected. However, in the absence of Cx32 protein, Cx26 did not participate in gap junction formation, leading to a complete lack of intercellular communication among Mist1KO acinar cells. Additional studies testing Mist1 gene constructs in pancreatic exocrine cells confirmed that Mist1 transcriptionally regulates expression of the Cx32 gene. We conclude that Mist1 functions as a positive regulator of Cx32 gene expression and, in its absence, acinar cell gap junctions and intercellular communication pathways become disrupted.
Key words: Pancreas, Exocytosis, bHLH, Transcription, Cell communication
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
|
|
 |
|
  B. J. Capoccia, W. J. Huh, and J. C. Mills How form follows functional genomics: gene expression profiling gastric epithelial cells with a particular discourse on the parietal cell Physiol Genomics, April 10, 2009; 37(2): 67 - 78. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Park, O. T. Shafer, S. P. Shepherd, H. Suh, J. S. Trigg, and P. H. Taghert The Drosophila Basic Helix-Loop-Helix Protein DIMMED Directly Activates PHM, a Gene Encoding a Neuropeptide-Amidating Enzyme Mol. Cell. Biol., January 1, 2008; 28(1): 410 - 421. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. L Pin, C. L Johnson, B. Rade, A. S Kowalik, V. C Garside, and M. E Everest Identification of a Transcription Factor, BHLHB8, Involved in Mouse Seminal Vesicle Epithelium Differentiation and Function Biol Reprod, January 1, 2008; 78(1): 91 - 100. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. S. Kowalik, C. L. Johnson, S. A. Chadi, J. Y. Weston, E. N. Fazio, and C. L. Pin Mice lacking the transcription factor Mist1 exhibit an altered stress response and increased sensitivity to caerulein-induced pancreatitis Am J Physiol Gastrointest Liver Physiol, April 1, 2007; 292(4): G1123 - G1132. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. G. Ramsey, J. M. Doherty, C. C. Chen, T. S. Stappenbeck, S. F. Konieczny, and J. C. Mills The maturation of mucus-secreting gastric epithelial progenitors into digestive-enzyme secreting zymogenic cells requires Mist1 Development, January 1, 2007; 134(1): 211 - 222. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Zhao, C. Johansson, T. Tran, R. Bettencourt, Y. Itahana, P.-Y. Desprez, and S. F. Konieczny Identification of a Basic Helix-Loop-Helix Transcription Factor Expressed in Mammary Gland Alveolar Cells and Required for Maintenance of the Differentiated State Mol. Endocrinol., September 1, 2006; 20(9): 2187 - 2198. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. A. Tuveson, L. Zhu, A. Gopinathan, N. A. Willis, L. Kachatrian, R. Grochow, C. L. Pin, N. Y. Mitin, E. J. Taparowsky, P. A. Gimotty, et al. Mist1-KrasG12D Knock-In Mice Develop Mixed Differentiation Metastatic Exocrine Pancreatic Carcinoma and Hepatocellular Carcinoma Cancer Res., January 1, 2006; 66(1): 242 - 247. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E N Fazio, M Everest, R Colman, R Wang, and C L Pin Altered Glut-2 accumulation and {beta}-cell function in mice lacking the exocrine-specific transcription factor, Mist1 J. Endocrinol., December 1, 2005; 187(3): 407 - 418. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Luo, D. M. Shin, X. Wang, S. F. Konieczny, and S. Muallem Aberrant Localization of Intracellular Organelles, Ca2+ Signaling, and Exocytosis in Mist1 Null Mice J. Biol. Chem., April 1, 2005; 280(13): 12668 - 12675. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Zhu, T. Tran, J. M. Rukstalis, P. Sun, B. Damsz, and S. F. Konieczny Inhibition of Mist1 Homodimer Formation Induces Pancreatic Acinar-to-Ductal Metaplasia Mol. Cell. Biol., April 1, 2004; 24(7): 2673 - 2681. [Abstract] [Full Text] [PDF]
|
|
