title: Endoplasmic Reticulum Calcium Regulates Epidermal Barrier Response and Desmosomal Structure.
abstract: Ca(2+) fluxes direct keratinocyte differentiation, cell-to-cell adhesion, migration, and epidermal barrier homeostasis. We previously showed that intracellular Ca(2+) stores constitute a major portion of the calcium gradient especially in the stratum granulosum. Loss of the calcium gradient triggers epidermal barrier homeostatic responses. In this report, using unfixed ex vivo epidermis and human epidermal equivalents we show that endoplasmic reticulum (ER) Ca(2+) is released in response to barrier perturbation, and that this release constitutes the major shift in epidermal Ca(2+) seen after barrier perturbation. We find that ER Ca(2+) release correlates with a transient increase in extracellular Ca(2+). Lastly, we show that ER calcium release resulting from barrier perturbation triggers transient desmosomal remodeling, seen as an increase in extracellular space and a loss of the desmosomal intercellular midline. Topical application of thapsigargin, which inhibits the ER Ca(2+) ATPase activity without compromising barrier integrity, also leads to desmosomal remodeling and loss of the midline structure. These experiments establish the ER Ca(2+) store as a master regulator of the Ca(2+) gradient response to epidermal barrier perturbation, and suggest that ER Ca(2+) homeostasis also modulates normal desmosomal reorganization, both at rest and after acute barrier perturbation.
authors.affiliation: Dermatology Service, Department of Veterans Affairs Medical Center, and Department of Dermatology, University of California, San Francisco, California, USA. Electronic address: Anna.celli2@ucsf.edu.
authors.forename: Anna
authors.initials: A
authors.lastname: Celli
authors.affiliation: Dermatology Service, Department of Veterans Affairs Medical Center, and Department of Dermatology, University of California, San Francisco, California, USA.
authors.forename: Debra
authors.initials: D
authors.lastname: Crumrine
authors.affiliation: Dermatology Service, Department of Veterans Affairs Medical Center, and Department of Dermatology, University of California, San Francisco, California, USA.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Meyer
authors.affiliation: Dermatology Service, Department of Veterans Affairs Medical Center, and Department of Dermatology, University of California, San Francisco, California, USA.
authors.forename: Theodora M
authors.initials: TM
authors.lastname: Mauro
mesh_terms: D000818:Animals; D001707:Biopsy, Needle; D002118:Calcium / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology; D003896:Desmosomes / Q000187:drug effects / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007150:Immunohistochemistry; D012869:Skin Absorption / Q000502:physiology*; D019284:Thapsigargin / Q000494:pharmacology*
chemical_list: D019284:Thapsigargin; D002118:Calcium