title: TRPV3 mutants causing Olmsted Syndrome induce impaired cell adhesion and nonfunctional lysosomes.
abstract: TRPV3 is a non-selective cationic channel and is important for several physiological functions. It can be activated by physiological temperature and selective endogenous and exogenous compounds. TRPV3 is one of the key ion channel involved in Ca2+-signaling in keratinocyte and thus involved in skin-related functions. Recently, naturally occurring mutations in TRPV3, namely G573A, G573S, G573C and W692G have been detected which are linked with the development of pathophysiological conditions such as Olmsted Syndrome (OS) and other skin disorders. Our qualitative and quantitative data suggests that these naturally occurring TRPV3 mutants are mainly restricted in the ER. Expression of OS-mutants cause impaired vesicular trafficking resulting reduced surface localization of these mutants and other membrane proteins too. OS-mutants also cause reduced cell adhesion, altered distribution and less number of lysosomes. Our data confirms that TRPV3 is a lysosomal protein suggesting that Olmsted Syndrome is a lysosomal disorder. These findings may have a broad implication in the context of keratinocyte functions, skin-degeneration and in skin-cancer.
authors.affiliation: a National Institute of Science Education and Research, Institute of Physics Campus , Bhubaneswar , Orissa , India.|b Homi Bhabha National Institute, Training School Complex , Mumbai , India.
authors.forename: Manoj
authors.initials: M
authors.lastname: Yadav
authors.affiliation: a National Institute of Science Education and Research, Institute of Physics Campus , Bhubaneswar , Orissa , India.|b Homi Bhabha National Institute, Training School Complex , Mumbai , India.
authors.forename: Chandan
authors.initials: C
authors.lastname: Goswami
mesh_terms: D002448:Cell Adhesion / Q000235:genetics*; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D015603:Keratinocytes / Q000473:pathology; D007645:Keratoderma, Palmoplantar / Q000235:genetics* / Q000473:pathology*; D008247:Lysosomes / Q000473:pathology*; D009154:Mutation; D021381:Protein Transport; D050916:TRPV Cation Channels / Q000235:genetics* / Q000378:metabolism
chemical_list: D050916:TRPV Cation Channels
keywords: Olmsted Syndrome; TRPV; keratinocytes; lysosomal disorder; skin; surface expression