Atypical Protein Kinase C Isoforms Differentially Regulate Directional Keratinocyte Migration During Wound Healing

Publication date: Available online 8 January 2019

Source: Journal of Dermatological Science

Author(s): Natsuko Noguchi, Tomonori Hirose, Tomoko Suzuki, Masami Kagaya, Kazuhiro Chida, Shigeo Ohno, Motomu Manabe, Shin-Ichi Osada

Abstract

Background

The epidermis possesses regenerative properties that become apparent only after wounding. Atypical protein kinase C (aPKC) isoforms aPKCζ and aPKCλ form a ternary complex with Par3 and Par6, and play crucial roles in establishing and maintaining epithelial cell polarity. The epidermal loss of aPKCλ results in progressive depletion of hair follicle stem cells. However, it is unclear whether aPKCs have equivalent activities in epidermal regeneration.

Objectives

To clarify functional differences between aPKCζ and aPKCλ in cutaneous wound healing.

Methods

We compared cutaneous wound healing processes in vivo using mutant mice with genetic deletion of each aPKC isoform. We also analyzed functional differences between aPKCζ and aPKCλ in cell proliferation, directional cell migration, and formation of microtubules in vitro using primary keratinocytes established from each mutant mouse.

Results

Wound healing was significantly retarded in epidermis-specific aPKCλ knockout mice. In aPKCλ-deleted keratinocytes, the correct orientation of cell protrusions toward the wound was disrupted through the destabilization of Par6β. The elongation of stabilized β-tubulin was also deteriorated in aPKCλ-deleted keratinocytes, leading to defects in cell spreading. Conversely, wound healing and directional cell migration in aPKCζ-deleted mice were comparable to those in their control littermates.

Conclusions

aPKCs are not functionally equivalent; aPKCλ, but not aPKCζ, plays a primary role in cutaneous wound healing.

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