Atypical protein kinase C isoforms differentially regulate directional keratinocyte migration during wound healing. 2019

Natsuko Noguchi, and Tomonori Hirose, and Tomoko Suzuki, and Masami Kagaya, and Kazuhiro Chida, and Shigeo Ohno, and Motomu Manabe, and Shin-Ichi Osada
Department of Dermatology & Plastic Surgery, Akita University Graduate School of Medicine, Akita, Japan.

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. OBJECTIVE 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.

UI MeSH Term Description Entries
D007527 Isoenzymes Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics. Alloenzyme,Allozyme,Isoenzyme,Isozyme,Isozymes,Alloenzymes,Allozymes
D011493 Protein Kinase C An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters. Calcium Phospholipid-Dependent Protein Kinase,Calcium-Activated Phospholipid-Dependent Kinase,PKC Serine-Threonine Kinase,Phospholipid-Sensitive Calcium-Dependent Protein Kinase,Protein Kinase M,Calcium Activated Phospholipid Dependent Kinase,Calcium Phospholipid Dependent Protein Kinase,PKC Serine Threonine Kinase,Phospholipid Sensitive Calcium Dependent Protein Kinase,Phospholipid-Dependent Kinase, Calcium-Activated,Serine-Threonine Kinase, PKC
D002465 Cell Movement The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell. Cell Migration,Locomotion, Cell,Migration, Cell,Motility, Cell,Movement, Cell,Cell Locomotion,Cell Motility,Cell Movements,Movements, Cell
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D004817 Epidermis The external, nonvascular layer of the skin. It is made up, from within outward, of five layers of EPITHELIUM: (1) basal layer (stratum basale epidermidis); (2) spinous layer (stratum spinosum epidermidis); (3) granular layer (stratum granulosum epidermidis); (4) clear layer (stratum lucidum epidermidis); and (5) horny layer (stratum corneum epidermidis).
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D014945 Wound Healing Restoration of integrity to traumatized tissue. Healing, Wound,Healings, Wound,Wound Healings
D015603 Keratinocytes Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell. Keratinocyte
D016764 Cell Polarity Orientation of intracellular structures especially with respect to the apical and basolateral domains of the plasma membrane. Polarized cells must direct proteins from the Golgi apparatus to the appropriate domain since tight junctions prevent proteins from diffusing between the two domains. Cell Polarities,Polarities, Cell,Polarity, Cell
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus

Related Publications

Natsuko Noguchi, and Tomonori Hirose, and Tomoko Suzuki, and Masami Kagaya, and Kazuhiro Chida, and Shigeo Ohno, and Motomu Manabe, and Shin-Ichi Osada
March 2016, Journal of cellular biochemistry,
Natsuko Noguchi, and Tomonori Hirose, and Tomoko Suzuki, and Masami Kagaya, and Kazuhiro Chida, and Shigeo Ohno, and Motomu Manabe, and Shin-Ichi Osada
May 2007, Frontiers in bioscience : a journal and virtual library,
Natsuko Noguchi, and Tomonori Hirose, and Tomoko Suzuki, and Masami Kagaya, and Kazuhiro Chida, and Shigeo Ohno, and Motomu Manabe, and Shin-Ichi Osada
January 2018, Methods in molecular biology (Clifton, N.J.),
Natsuko Noguchi, and Tomonori Hirose, and Tomoko Suzuki, and Masami Kagaya, and Kazuhiro Chida, and Shigeo Ohno, and Motomu Manabe, and Shin-Ichi Osada
September 2021, eLife,
Natsuko Noguchi, and Tomonori Hirose, and Tomoko Suzuki, and Masami Kagaya, and Kazuhiro Chida, and Shigeo Ohno, and Motomu Manabe, and Shin-Ichi Osada
May 2008, Journal of applied physiology (Bethesda, Md. : 1985),
Natsuko Noguchi, and Tomonori Hirose, and Tomoko Suzuki, and Masami Kagaya, and Kazuhiro Chida, and Shigeo Ohno, and Motomu Manabe, and Shin-Ichi Osada
January 2011, International journal of biological sciences,
Natsuko Noguchi, and Tomonori Hirose, and Tomoko Suzuki, and Masami Kagaya, and Kazuhiro Chida, and Shigeo Ohno, and Motomu Manabe, and Shin-Ichi Osada
February 2015, Biochemical and biophysical research communications,
Natsuko Noguchi, and Tomonori Hirose, and Tomoko Suzuki, and Masami Kagaya, and Kazuhiro Chida, and Shigeo Ohno, and Motomu Manabe, and Shin-Ichi Osada
January 2016, Journal of diabetes research,
Natsuko Noguchi, and Tomonori Hirose, and Tomoko Suzuki, and Masami Kagaya, and Kazuhiro Chida, and Shigeo Ohno, and Motomu Manabe, and Shin-Ichi Osada
January 1998, Advances in experimental medicine and biology,
Natsuko Noguchi, and Tomonori Hirose, and Tomoko Suzuki, and Masami Kagaya, and Kazuhiro Chida, and Shigeo Ohno, and Motomu Manabe, and Shin-Ichi Osada
September 1993, Journal of cellular physiology,
Copied contents to your clipboard!