title: Identification of a keratin-associated protein with a putative role in vesicle transport.
abstract: Protection of skin against UV light requires a coordinated interaction between melanocytes and keratinocytes. Melanosomes are lysosome-related organelles that originate in melanocytes and are transferred into keratinocytes where they form a supranuclear cap. The mechanism responsible for melanosome transfer into keratinocytes and their intracellular distribution is poorly understood. Recently, we reported for the first time that loss-of-function mutations in the keratin K5 gene affect melanosome distribution in keratinocytes and results in a reticulate hyperpigmentation disorder, called Dowling-Degos disease. Here, we characterise the distribution and behaviour of individual K5 and K14 domains following transient and stable transfection into cells. We report that the K5 head domain is considerably more stable than the K14 head. Moreover, the distribution of the K5 head domain is altered following depolymerisation of microtubules. Following co-immunoprecipitation, we verified a specific interaction between the head domain of K5 with Hsc70, a chaperone also involved in vesicle uncoating. We hypothesise that this interaction is involved in melanosome formation or transport in keratinocytes. Alternatively, it may have a general function in the regulation of keratin assembly.
authors.affiliation: Institut für Physiologische Chemie, Abteilung für Zellbiochemie, Bonner Forum Biomedizin und LIMES, Rheinische Friedrich-Wilhelms-Universität, Nussallee 11, D-53115 Bonn, Germany.
authors.forename: Laura
authors.initials: L
authors.lastname: Planko
authors.forename: Karsten
authors.initials: K
authors.lastname: Böhse
authors.forename: Jörg
authors.initials: J
authors.lastname: Höhfeld
authors.forename: Regina C
authors.initials: RC
authors.lastname: Betz
authors.forename: Sandra
authors.initials: S
authors.lastname: Hanneken
authors.forename: Sibylle
authors.initials: S
authors.lastname: Eigelshoven
authors.forename: Roland
authors.initials: R
authors.lastname: Kruse
authors.forename: Markus M
authors.initials: MM
authors.lastname: Nöthen
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Magin
mesh_terms: D000199:Actins / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects; D045744:Cell Line, Tumor; D003896:Desmosomes / Q000187:drug effects / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D050883:HSC70 Heat-Shock Proteins / Q000378:metabolism*; D006238:Haploidy; D006801:Humans; D053547:Keratin-14 / Q000737:chemistry / Q000378:metabolism; D053555:Keratin-5 / Q000737:chemistry / Q000378:metabolism; D008164:Luminescent Proteins / Q000378:metabolism; D020460:Melanosomes / Q000187:drug effects / Q000378:metabolism; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D015739:Nocodazole / Q000494:pharmacology; D009685:Nuclear Envelope / Q000187:drug effects / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D017434:Protein Structure, Tertiary; D012867:Skin / Q000187:drug effects / Q000473:pathology; D022161:Transport Vesicles / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000199:Actins; D001426:Bacterial Proteins; D050883:HSC70 Heat-Shock Proteins; D053547:Keratin-14; D053555:Keratin-5; D008164:Luminescent Proteins; D009687:Nuclear Proteins; C054562:yellow fluorescent protein, Bacteria; D015739:Nocodazole