Myosin Va belongs to the unconventional myosin family that has been identified in many non-muscle tissues of vertebrates and invertebrates. All known myosins bind actin and produce mechanical force through ATP hydrolysis. Myosin Va is only expressed in melanocytes and in cells of the neuronal system (Mercer et al., 1991). In melanocytes it is part of the melanosome transport complex (Wu et al.,...

Human cells contain more than 60 Ras-like, Rab GTPases that are localized to the surfaces of distinct membrane-bound compartments. Rabs are master regulators of membrane traffic events: they can catalyze the formation of membrane microdomains, the collection of cargo into transport vesicles, the motility of vesicles along cytoskeletal tracks, the docking of vesicles with their targets, and the ...

Natural killer (NK) cells form a subset of lymphocytes that play a key role in immuno-surveillance and host defense against cancer and viral infections. They recognize stressed cells through a variety of germline-encoded activating cell surface receptors and utilize their cytotoxic ability to eliminate abnormal cells. Killing of target cells is a complex, multi-stage process that concludes in t...

Regulated secretory pathways are highly developed in multicellular organisms as a means of intercellular communication. Each of these pathways harbors unique store organelles, such as granules in endocrine and exocrine tissues and melanosomes in melanocytes. It has recently been shown that the monomeric GTPase Rab27 subfamily regulates the exocytosis of these cell-specific store organelles. Fur...

Griscelli syndrome (GS) is a rare autosomal recessive disorder that associates hypopigmentation, characterized by a silver-gray sheen of the hair and the presence of large clusters of pigment in the hair shaft, and the occurrence of either a primary neurological impairment or a severe immune disorder. Two different genetic forms, GS1 and GS2, respectively, account for the mutually exclusive neu...

BACKGROUND The motor protein myosin Va plays an important role in the trafficking of intracellular vesicles. Mutation of the Myo5a gene causes Griscelli syndrome type 1 in humans and the dilute phenotype in mice, which are both characterised by pigment dilution and neurological defects as a result of impaired vesicle transport in melanocytes and neuroendocrine cells. The role of myosin Va in pl...

Griscelli syndrome type 2 (GS2) is a genetic disorder in which patients exhibit life-threatening defects of cytotoxic T lymphocytes (CTLs) whose lytic granules fail to dock on the plasma membrane and therefore do not release their contents. The disease is caused by the absence of functional rab27a, but how rab27a controls secretion of lytic granule contents remains elusive. Mutations in Munc13-...

BACKGROUND Microscopic examination of scalp hair can provide important diagnostic information in a range of paediatric conditions. It is a non-invasive and cost effective investigation, which is not widely performed. AIMS To examine retrospectively the value of hair examination by light microscopy, including polarising microscopy, in a specialist paediatric pathology department during a 15 ye...

BACKGROUND Retroviruses have been observed to bud intracellularly into multivesicular bodies (MVB), in addition to the plasma membrane. Release from MVB is thought to occur by Ca(2+)-regulated fusion with the plasma membrane. PRINCIPAL FINDINGS To address the role of the MVB pathway in replication of the murine leukemia virus (MLV) we took advantage of mouse models for the Hermansky-Pudlak sy...

Mutations of the myosin Va gene cause the neurological diseases Griscelli syndrome type 1 and Elejalde syndrome in humans and dilute phenotypes in rodents. To understand the pathophysiological mechanisms underlying the neurological disorders in myosin Va diseases, we conducted an integrated analysis at the molecular, cellular, electrophysiological, and behavioral levels using the dilute-neurolo...