title: Rab27b is up-regulated in human Griscelli syndrome type II melanocytes and linked to the actin cytoskeleton via exon F-Myosin Va transcripts.
abstract: Patients with the autosomal recessive Griscelli-Pruniéras syndrome type II are immunologically impaired and have an unusual silvery-grey hypopigmented colour of scalp hair, eyelashes and eyebrows but no noteworthy pigmentary abnormalities of the skin. In most Griscelli patients, the RAB27A gene, which encodes a small GTPase that is associated with the melanosome membrane in melanocytes, is mutated. Here we discuss a genomic RAB27A deletion found in a 21-month-old Moroccan Griscelli patient. Additionally, we provide evidence that the loss of functional Rab27a in melanocytes of this Griscelli patient is partially compensated by the up-regulation of Rab27b, a homologue of Rab27a. By real-time quantitative PCR and western blot analysis, we found that Rab27b mRNA and protein, expressed at low levels in normal human melanocytes, is significantly up-regulated in melanocytes derived from this patient. Our immunofluorescence and yeast two-hybrid screening studies reveal that Rab27b can form a tripartite complex on the melanosome membrane with Melanophilin, a Rab27a effector, and protein products of Myosin Va transcripts that contain exon F. Our data suggest that up-regulated Rab27b in melanocytes of the Griscelli patient can partially take over the function of Rab27a, which could explain the fact that this patient had an evenly pigmented skin and was able to tan.
authors.affiliation: Department of Dermatology, Ghent University Hospital, De Pintelaan 185, Gent, Belgium.
authors.forename: Wendy
authors.initials: W
authors.lastname: Westbroek
authors.forename: Jo
authors.initials: J
authors.lastname: Lambert
authors.forename: Sofie
authors.initials: S
authors.lastname: De Schepper
authors.forename: Robert
authors.initials: R
authors.lastname: Kleta
authors.forename: Karolien
authors.initials: K
authors.lastname: Van Den Bossche
authors.forename: Miguel C
authors.initials: MC
authors.lastname: Seabra
authors.forename: Marjan
authors.initials: M
authors.lastname: Huizing
authors.forename: Mieke
authors.initials: M
authors.lastname: Mommaas
authors.forename: Jean Marie
authors.initials: JM
authors.lastname: Naeyaert
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000417:Albinism / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002352:Carrier Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D005091:Exons; D017353:Gene Deletion; D006801:Humans; D020460:Melanosomes / Q000378:metabolism* / Q000473:pathology; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism*; D024701:Myosin Type V / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020798:Two-Hybrid System Techniques; D015854:Up-Regulation / Q000235:genetics*; D020691:rab GTP-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D000075745:rab27 GTP-Binding Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C492410:MLPH protein, human; D012333:RNA, Messenger; D000075745:rab27 GTP-Binding Proteins; C077511:MYO5A protein, human; D024701:Myosin Type V; C066694:RAB27A protein, human; C512960:Rab27B protein, human; D018995:Myosin Heavy Chains; D020691:rab GTP-Binding Proteins