■綜説
細胞極性制御因子aPKCの毛包幹細胞の維持，および創傷治癒における役割
長田 真一
日本医科大学多摩永山病院皮膚科
The Role of Cell Polarity Regulator aPKC in Hair Follicle Stem Cell Maintenance and Wound Healing
Shin-Ichi Osada
Department of Dermatology, Nippon Medical School Tama Nagayama Hospital
The protein kinase C (PKC) family is a group of serine/threonine kinases that mediate intracellular signaling activated by growth factor receptors, tyrosine kinase receptors, and G-protein coupled receptors through lipid-derived secondary messengers. In mammals, the PKC family is composed of the following three structurally and functionally distinct subgroups: conventional PKCs (cPKC; α, βI/II, and γ), novel PKCs (nPKC; δ, ε, η, and θ), and atypical PKCs (aPKC; ζ and ι/λ; λ in mice). Among the PKC family members, aPKCs play essential roles in establishing epithelial cell polarity by interacting with partition-defective (Par) proteins, Par3 and Par6, which were first identified in genetic screening for regulators of asymmetric division in the early embryo of Caenorhabditis elegans. The aPKC-Par3-Par6 ternary complex is evolutionarily conserved and is implicated in a variety of cell polarity events. To clarify functional differences between aPKCζ and aPKCλ in the stratified epidermis in vivo, we have generated mutant mice with genetic deletion of each aPKC isoform. Epidermis-specific aPKCλ conditionally knockout mice (aPKCλ cKO) showed progressive hair loss, abnormal hair cycling, a gradual decrease of hair follicle stem cell (HFSC) population, and loss of the HFSC quiescence. In addition, cutaneous wound healing was significantly retarded in aPKCλ cKO mice, and the correct orientation of cell protrusions toward the wound was disrupted in aPKCλ-deleted keratinocytes, through the destabilization of Par6β. Conversely, HFSC maintenance, wound healing, and directional cell migration in aPKCζ-deleted mice were comparable to those in their control littermates. These results indicate that aPKCs are not functionally equivalent; aPKCλ, but not aPKCζ, plays a primary role in maintaining HFSC population and cutaneous wound healing.
日医大医会誌 2020; 16(3), 130-137
Key words
aPKC, Par, cell polarity, hair follicle stem cells, wound healing
Correspondence to
Shin-Ichi Osada, Department of Dermatology, Nippon Medical School Tama Nagayama Hospital, 1-7-1 Nagayama, Tama, Tokyo 206-8512, Japan
E-mail：osada0130@nms.ac.jp
受付：2020年4月21日 受理：2020年5月27日 |
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