Mechanisms of protein delivery to melanosomes in pigment cells - PubMed (original) (raw)

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Mechanisms of protein delivery to melanosomes in pigment cells

Anand Sitaram et al. Physiology (Bethesda). 2012 Apr.

Abstract

Vertebrate pigment cells in the eye and skin are useful models for cell types that use specialized endosomal trafficking pathways to partition cargo proteins to unique lysosome-related organelles such as melanosomes. This review describes current models of protein trafficking required for melanosome biogenesis in mammalian melanocytes.

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Figures

Figure 1

Figure 1. Melanosome maturation and segregation from endocytic organelles

Represented are maturation stages of endosomes (left) and melanosomes (right) from early endosomes (top) and their putative derivation by maturation from earlier compartments (red arrows). Protein contents of melanosomes as described in the text are indicated in italics to the right. Early endosomes (top) form by coalescence of membranes derived by internalization from the plasma membrane and by input from the secretory pathway. They consist of tubular domains and vacuolar domains; within the vacuolar domains, internal vesicles begin to form by invaginationof the limiting membrane in regions rich in bilayered clathrin-and Hrs-containing coats (black arrows). The vacuolar domains mature into late endosomal multivesicularbodies (MVB) as in other cell types by exchange with other compartments via tubular connections. Lumenal contents of late endosomes are degraded upon fusion with lysosomes. In pigment cells, the vacuolar domains of early endosomes also correspond to StageI melanosomes, but are distinguished from vacuolar early endosomes of other cells by the presence of fibrils emanating from the internal vesicles (arrowheads). These fibrils elongate and assemble into sheets in Stage II melanosomes. Delivery of contents to Stage II melanosomes by vesicular traffic (not shown) or by tubular intermediates from early endosomes (as shown) results in the deposition of melanins on the fibrils in Stage III melanosomes. Continued melanin deposition masks internal structure in Stage IV melanosomes.

Figure 2

Figure 2. Model of delivery of selected cargoes to late-stage melanosomes

Adaptor proteins AP-1 and AP-3 concentrate specific melanosomal integral membrane cargo proteins such as OCA2 (blue bars), TYRP1 (pink bars) and tyrosinase (gold bars) within early endosomes. AP-1 also engages the microtubule plus-end directed kinesin KIF13A to establish tubules that emanate from recycling endosomal domains in the cell periphery and fuse with the membrane of nearby melanosomes. AP-1 and perhaps AP-3 direct cargoes such as OCA2 and TYRP1 into this pathway. BLOC-1 also functions on this pathway during cargo entry into the tubules. BLOC-2 and RAB38 appear to act downstream, perhaps to specify the targeting of these tubules to melanosomes. Engagement ofcargo proteins on the tubules with AP-1 or AP-3 might be required for efficient delivery of cargoes from the tubules to the melanosome. AP-3 also functions from a distinct domain of early endosomes to direct BLOC-1-independent vesicular trafficking of TYR to the melanosome. RAB38 and perhaps BLOC-2 facilitate melanosomal targeting in this pathway. This figure is modified from Figure 8 of Delevoye et al., 2009, originally published in Journal of Cell Biology, vol. 187, pp. 247–264 (35).

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References

    1. Anderson PD, Huizing M, Claassen DA, White J, Gahl WA. Hermansky-Pudlak syndrome type 4 (HPS-4): clinical and molecular characteristics. Hum. Genet. 2003;113(1):10–17. 10–7. - PubMed
    1. Angers CG, Merz AJ. HOPS interacts with Apl5 at the vacuole membrane and is required for consumption of AP-3 transport vesicles. Mol. Biol. Cell. 2009;20:4563–4574. - PMC - PubMed
    1. Aydin IT, Hummler E, Smit NP, Beermann F. Coat color dilution in mice because of inactivation of the melanoma antigen MART-1. Pigment Cell Melanoma Res. 2012;25:37–46. - PubMed
    1. Barral DC, Seabra MC. The melanosome as a model to study organelle motility in mammals. Pigment Cell Melanoma Res. 2004;17:111–118. - PubMed
    1. Bassi MT, Schiaffino MV, Renieri A, De Nigris F, Galli L, Bruttini M, Gebbia M, Bergen AA, Lewis RA, Ballabio A. Cloning of the gene for ocular albinism type 1 from the distal short arm of the X chromosome. Nature Genet. 1995;10:13–19. - PubMed

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