title: GPHR-dependent functions of the Golgi apparatus are essential for the formation of lamellar granules and the skin barrier.
abstract: The lumen of the Golgi apparatus is regulated to be weakly acidic, which is critical for its functions. The Golgi pH regulator (GPHR) is an anion channel essential for normal acidification of the Golgi apparatus, and is therefore required for its functions. The Golgi apparatus has been thought to be the origin of lamellar granules in the skin. To study the functional role(s) of GPHR in the skin, we established keratinocyte-specific GPHR-knockout mice using the Cre-loxP system. These mutant mice exhibited hypopigmented skin, hair loss, and scaliness. Histological examination of GPHR-knockout mice showed ballooning of the basal cells and follicular dysplasia. In addition, inflammatory cells were seen in the dermis. The expression of trans-Golgi network 46, a marker for lamellar bodies, and kallikrein 7, a protein within lamellar bodies, is diminished in GPHR-knockout mouse skin. Examination by electron microscopy revealed that keratinocytes produced aberrant lamellar bodies. The transepidermal water loss of these knockout mice was increased compared with wild-type mice. Moreover, expression of cathelicidin-related antimicrobial peptide (CRAMP) in the skin was diminished. These results suggest that GPHR is essential for the homeostasis of the epidermis including the formation of lamellar bodies and for the barrier function.
authors.affiliation: Department of Dermatology, Kochi Medical School, Kochi University, Nankoku, Japan. tarutani@kochi-u.ac.jp
authors.forename: Masahito
authors.initials: M
authors.lastname: Tarutani
authors.forename: Kimiko
authors.initials: K
authors.lastname: Nakajima
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Uchida
authors.forename: Mikiro
authors.initials: M
authors.lastname: Takaishi
authors.forename: Naoko
authors.initials: N
authors.lastname: Goto-Inoue
authors.forename: Masahito
authors.initials: M
authors.lastname: Ikawa
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Setou
authors.forename: Taroh
authors.initials: T
authors.lastname: Kinoshita
authors.forename: Peter M
authors.initials: PM
authors.lastname: Elias
authors.forename: Shigetoshi
authors.initials: S
authors.lastname: Sano
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Maeda
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins / Q000378:metabolism; D002454:Cell Differentiation; D006056:Golgi Apparatus / Q000378:metabolism*; D007249:Inflammation; D007473:Ion Channels / Q000737:chemistry; D007610:Kallikreins / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D008957:Models, Genetic; D012867:Skin / Q000378:metabolism*
chemical_list: D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; D007473:Ion Channels; D008562:Membrane Glycoproteins; C513046:Tgoln2 protein, mouse; D007610:Kallikreins; C495974:Klk7 protein, mouse