# Mechanisms of Gap Junction Regulation

> **NIH NIH R01** · UNIVERSITY OF NEBRASKA MEDICAL CENTER · 2022 · $497,966

## Abstract

Abstract:
 Gap junctions are integral membrane proteins that enable the direct cytoplasmic exchange of ions and low
molecular-mass metabolites between adjacent cells. They provide a pathway for propagating and/or amplifying
the signal transduction cascades triggered by cytokines, growth factors, and other cell signaling molecules
involved in growth regulation and development. Dysfunctional intercellular communication via gap junctions has
been implicated in causing many human diseases. The objective of this project is to use a multi-disciplinary
approach to identify the key intrinsic regulatory mechanisms that are responsible for Cx43 and Cx45 function.
The central hypothesis is that unique intermolecular interactions within the divergent CT domain of connexins
affect gap junction regulation. More specifically, we hypothesize that after myocardial infarction, differential
regulation of Cx43 and Cx45 involves specific phosphorylations and protein interactions of their CT domain. The
significance of this proposal is that discovery of how interactions mediated by the CT domain can be modulated
would open the door to strategies to ameliorate pathological effects of altered connexin regulation in the failing
heart. The following Specific Aims are proposed to investigate this concept: 1) What drives Cx43 away from gap
junctions/intercalated discs in vitro and in a murine model of myocardial infarction? and 2) What promotes Cx45
gap junction/intercalated disc localization and is Cx45 expression in left ventricle hypertrophy after myocardial
infarction an arrhythmogenic substrate? Upon completion of this project, we expect to describe novel
mechanisms by which phosphorylation and protein partners regulate Cx43 and Cx45 function and strategies by
which the pathological effects of Pyk2, Src, and Cx45 upregulation in failing hearts may be lessened.

## Key facts

- **NIH application ID:** 10489303
- **Project number:** 5R01GM072631-15
- **Recipient organization:** UNIVERSITY OF NEBRASKA MEDICAL CENTER
- **Principal Investigator:** PAUL L SORGEN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $497,966
- **Award type:** 5
- **Project period:** 2006-06-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10489303

## Citation

> US National Institutes of Health, RePORTER application 10489303, Mechanisms of Gap Junction Regulation (5R01GM072631-15). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10489303. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*