ZO-1 determines adherens and gap junction localization at intercalated disks
Joseph A Palatinus1, Michael P O'Quinn, Ralph J Barker
1Department of Regenerative Medicine and Cell Biology, Cardiovascular Biology Center, Medical University of South Carolina, 173 Ashley Ave., Charleston, SC, 29425, USA.
American Journal of Physiology. Heart and Circulatory Physiology
|December 7, 2010
Summary
Zonula occludens-1 (ZO-1) protein is crucial for organizing cardiac cell junctions. Disrupting ZO-1 causes gap junctions (GJs) and adherens junctions (AJs) to mislocalize, impacting cardiac health.
Area of Science:
- Cardiovascular Biology
- Cell Biology
- Molecular Cardiology
Background:
- Disruption of cardiac electromechanical junctions at myocyte-intercalated disks (ICDs) is linked to cardiac diseases.
- The precise role of zonula occludens-1 (ZO-1) in organizing these junctions remains unclear.
Purpose of the Study:
- To investigate the function of ZO-1 in regulating the spatial organization of gap junctions (GJs) and adherens junctions (AJs) at ICDs.
- To determine how ZO-1 influences the localization of junctional proteins within cardiac myocytes.
Main Methods:
- Expression of a dominant-negative ZO-1 construct (DN-ZO-1) in rat ventricular myocytes (VMs) in vitro and in vivo.
- Assays included colocalization, coimmunoprecipitation, and analysis of GJ and AJ protein distribution.
Main Results:
- DN-ZO-1 expression disrupted ZO-1 and N-cadherin interaction, leading to cytoplasmic internalization of AJ and GJ proteins.
- A breakdown in the characteristic pattern of GJ size and distribution at ICDs was observed.
- ZO-1 disruption resulted in altered connexin-43 (Cx43) localization, with increased lateralized and cytoplasmic Cx43.
Conclusions:
- ZO-1 regulates GJ localization through its association with the N-cadherin multiprotein complex.
- This ZO-1-N-cadherin interaction is essential for the stable localization of both AJs and GJs at ICDs.
- ZO-1 dysfunction contributes to the spatial disorganization of cardiac cell junctions observed in disease states.
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