PMID- 12829745
OWN - NLM
STAT- MEDLINE
DCOM- 20040519
LR  - 20231213
IS  - 0021-9533 (Print)
IS  - 0021-9533 (Linking)
VI  - 116
IP  - Pt 16
DP  - 2003 Aug 15
TI  - Exocrine specific expression of Connexin32 is dependent on the basic 
      helix-loop-helix transcription factor Mist1.
PG  - 3315-25
AB  - 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.
FAU - Rukstalis, J Michael
AU  - Rukstalis JM
AD  - Department of Biological Sciences, Purdue University, West Lafayette, IN 
      47907-1392, USA.
FAU - Kowalik, Agnes
AU  - Kowalik A
FAU - Zhu, Liqin
AU  - Zhu L
FAU - Lidington, Darcy
AU  - Lidington D
FAU - Pin, Christopher L
AU  - Pin CL
FAU - Konieczny, Stephen F
AU  - Konieczny SF
LA  - eng
GR  - R01 DK055489/DK/NIDDK NIH HHS/United States
GR  - AR41115/AR/NIAMS NIH HHS/United States
GR  - DK55489/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20030626
PL  - England
TA  - J Cell Sci
JT  - Journal of cell science
JID - 0052457
RN  - 0 (Basic Helix-Loop-Helix Transcription Factors)
RN  - 0 (Bhlha15 protein, mouse)
RN  - 0 (Connexins)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Animals
MH  - Basic Helix-Loop-Helix Transcription Factors
MH  - Cell Communication/*physiology
MH  - Connexins/*biosynthesis/physiology
MH  - Exocrine Glands/metabolism/physiopathology
MH  - Exocytosis/physiology
MH  - Gap Junctions/*metabolism/physiology
MH  - Gene Expression Regulation
MH  - Immunohistochemistry
MH  - Mice
MH  - Mice, Knockout
MH  - Pancreas/metabolism/physiopathology
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Transcription Factors/*metabolism/physiology
MH  - Transcription, Genetic/genetics
MH  - Gap Junction beta-1 Protein
EDAT- 2003/06/28 05:00
MHDA- 2004/05/20 05:00
CRDT- 2003/06/28 05:00
PHST- 2003/06/28 05:00 [pubmed]
PHST- 2004/05/20 05:00 [medline]
PHST- 2003/06/28 05:00 [entrez]
AID - jcs.00631 [pii]
AID - 10.1242/jcs.00631 [doi]
PST - ppublish
SO  - J Cell Sci. 2003 Aug 15;116(Pt 16):3315-25. doi: 10.1242/jcs.00631. Epub 2003 Jun 
      26.