Leader cell PLCγ1 activation during keratinocyte collective migration is induced by EGFR localization and clustering
Year: 2019
Type: article
Abstract: Re-epithelialization is a critical step in wound healing and results from the collective migration of keratinocytes. Previous work demonstrated that immobilized, but not soluble, epidermal growth factor (EGF) resulted in leader cell-specific activation of phospholipase C gamma 1 (PLCγ1) in HaCaT keratinocytes, and that this PLCγ1 activation was necessary to drive persistent cell migration. To determine the mechanism responsible for wound edge-localized PLCγ1 activation, we examined differences in cell area, cell-cell interactions, and EGF receptor (EGFR) localization between wound edge and bulk cells treated with vehicle, soluble EGF, or immobilized EGF. Our results support a multistep mechanism where EGFR translocation from the lateral membrane to the basolateral/basal membrane allows clustering in response to immobilized EGF. This analysis of factors regulating PLCγ1 activation is a crucial step toward developing therapies or wound dressings capable of modulating this signal and, consequently, cell migration.
DOI: 10.1002/btm2.10138
Authors: Chloe S. Kim, Xinhai Yang, Sarah Jacobsen, Kristyn S. Masters, Pamela K. Kreeger
Language: English
Topic: Wound Healing and Treatments
Subfield: Rehabilitation
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $1,800
OpenAlex ID: W2951029009
