Autoregulation of Connexin43 Gap Junction Formation by Internally Translated Isoforms

• DOI: 10.1016/j.celrep.2013.10.009
• Publication Date: 2013-11-07T12:01:30Z
• Authors: James W. Smyth; Robin M. Shaw
• Keywords: Eukaryotic translation; Heart beat

During each heartbeat, intercellular electrical coupling via connexin43 (Cx43) gap junctions enables synchronous cardiac contraction. In failing hearts, impaired Cx43 trafficking reduces junction coupling, resulting in arrhythmias. Here we report that internal translation within (GJA1) mRNA occurs, truncated isoforms autoregulate trafficking. We find at least four occur the human heart, with a 20 kDa isoform predominating. In-frame AUG codons GJA1 are initiation sites and their ablation arrests of full-length Cx43. The is sufficient to rescue this defect trans, suggesting it as chaperone for Limiting cap-dependent through inhibition mTOR enhances expression, increasing size. results suggest mechanism membrane protein autoregulation potent target therapies aimed restoring normal diseased hearts.