PKCμ promotes keratinocyte cell migration through Cx43 phosphorylation-mediated suppression of intercellular communication

Renju Pun; Ann M Cavanaugh; Emily Aldrich; Olivia Tran; Justin C Rudd; Laura A Hansen; Brian J North

doi:10.1016/j.isci.2024.109033

PKCμ promotes keratinocyte cell migration through Cx43 phosphorylation-mediated suppression of intercellular communication

iScience. 2024 Jan 29;27(3):109033. doi: 10.1016/j.isci.2024.109033. eCollection 2024 Mar 15.

Authors

Renju Pun¹, Ann M Cavanaugh², Emily Aldrich¹, Olivia Tran¹, Justin C Rudd¹, Laura A Hansen¹, Brian J North¹

Affiliations

¹ Biomedical Sciences Department, School of Medicine, Creighton University, Omaha, NE 68178, USA.
² Department of Biology, College of Arts and Sciences, Creighton University, Omaha, NE 68178, USA.

Abstract

Downregulation of intercellular communication through suppression of gap junctional conductance is necessary during wound healing. Connexin 43 (Cx43), a prominent gap junction protein in skin, is downregulated following wounding to restrict communication between keratinocytes. Previous studies found that PKCμ, a novel PKC isozyme, regulates efficient cutaneous wound healing. However, the molecular mechanism by which PKCμ regulates wound healing remains unknown. We have identified that PKCμ suppresses intercellular communication and enhances cell migration in an in vitro wound healing model by regulating Cx43 containing gap junctions. PKCμ can directly interact with and phosphorylate Cx43 at S368, which leads to Cx43 internalization and downregulation. Finally, utilizing phosphomimetic and non-phosphorylatable S368 substitutions and gap junction inhibitors, we confirmed that PKCμ regulates intercellular communication and in vitro wound healing by controlling Cx43-S368 phosphorylation. These results define PKCμ as a critical regulator of Cx43 phosphorylation to control cell migration and wound healing in keratinocytes.

Keywords: Biological sciences; Cell biology; Molecular biology; Molecular interaction.