Kinase programs spatiotemporally regulate gap junction assembly and disassembly: Effects on wound repair.

Abstract

Gap junctions are highly ordered plasma membrane domains that are constantly assembled, remodeled and turned over due to the short half-life of connexins, the integral membrane proteins that form gap junctions. Connexin 43 (Cx43), by far the most widely expressed connexin, is phosphorylated at multiple serine residues in the cytoplasmic, C-terminal region allowing for exquisite cellular control over gap junctional communication. This is evident during epidermal wounding where spatiotemporal changes in connexin expression occur as cells are instructed whether to die, proliferate or migrate to promote repair. Early gap junctional communication is required for initiation of keratinocyte migration, but accelerated Cx43 turnover is also critical for proper wound healing at later stages. These events are controlled via a "kinase program" where sequential phosphorylation of Cx43 leads to reductions in Cx43's half-life and significant depletion of gap junctions from the plasma membrane within several hours. The complex regulation of gap junction assembly and turnover affords several steps where intervention might speed wound healing.

• Authors: Joell L Solan, Paul D Lampe
• Journal: Seminars in cell & developmental biology (Semin Cell Dev Biol) Vol. 50 Pg. 40-8 (Feb 2016) ISSN: 1096-3634 [Electronic] England
• PMID: 26706150 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Review)
• Copyright: Copyright © 2015 Elsevier Ltd. All rights reserved.

Chemical References

• Connexin 43
• Protein Kinases

Topics

• Animals
• Connexin 43 (chemistry, metabolism)
• Gap Junctions (metabolism)
• Humans
• Models, Biological
• Phosphorylation
• Protein Kinases (metabolism)
• Wound Healing