The Dilute Locus and Griscelli Syndrome: Gateways Towards a Better Understanding of Melanosome Transport

Abstract

would present a major breakthrough in the possibilities to In this review an overview of recent advances in the understanding of melanosome movement within epidermal influence pigmentation and related disorders, of great concern melanocytes is given. Exploration of the molecular events to some patients. Moreover, melanosome transport offers a good model to study mammalian organelle trafficking and its involved in and determining the process of melanosome transkey players in general. port, as an essential part of human pigmentation, could lead to the identification of agents that augment, or down-regulate the Key words: Actin, Melanocyte, Motor proteins, Tubulin transfer of melanosomes to surrounding keratinocytes. This in melanosome transport has stagnated somewhat, and the focus was aimed at new molecular families involved in vesicle trafficking. Starting from an overview of the knowledge obtained with relation to molecular motors, the newly discovered involvement and co-operation of other molecules will be summarized in this review. Finally, this collection of findings is depicted graphically in Fig. 1.

Biogenesis of pigment granules: a sensitive way to regulate melanocyte function

“…The molecular motors involved in intracellular transport usually rely on the function of F-actin and/or myosin, and melanosomes are no exception [42,43]. In fact, the movement of melanosomes from the perinuclear region to the extremities of melanocytes (necessary for the subsequent transfer of melanosomes to neighboring keratinocytes) relies both on F-actin and on tubulin.…”

An overview on congenital alopecia in domestic animals

“…In mice, there are three spontaneous mutations at the d locus that cause coat colour dilution and similar histomorphological changes as seen in CDA and BHFD. These are mutations in the leaden (ln, chromosome 1), the dilute (d, chromosome 9), and the ashen gene, 148 corresponding to the human Griscelli syndrome, a rare autosomal recessive disorder that is characterized by diffuse skin pigmentation, silvery hair, and the occurrence of either a primary neurological impairment or a severe immune disorder 149 . It has been shown that those three mutations are linked to defects in the intracellular transport mechanisms within cutaneous melanocytes.…”

Disorders of Vesicles of Lysosomal Lineage: The Hermansky- Pudlak Syndromes

“…This disease includes partial oculocutaneous albinism, with characteristic pigment clumping in hair shafts, and either neurological involvement or haemophagocytic syndrome, a process of uncontrolled T lymphocyte and macrophage activation leading to death in the absence of bone marrow transplantation. Recent evidence indicates that Griscelli syndrome results from mutations in the genes coding for either the unconventional myosin Va or the small GTPase rab27a [19][20][21]. Both of these proteins operate in the actin-rich periphery of melanocytes, where the head domain of myosin Va binds to actin filaments [7].…”