New Perspectives on Melanoma_ The Role of PAX3

New Perspectives on Melanoma The Role of PAX3

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Unformatted text preview: enal fibrils of stage II melanosomes [89,92‐94]. Stage I melanosomes also contain MLANA, required for proper function 13 Chapter I – Thesis Overview of PMEL and melanosome maturation [95,96]. The melanogenic enzymes TYR and TYRP1 are delivered to stage II melanosomes via secretory pathway from the Golgi complex and early endosomes (Figure 1.1.7.) [88,89]. Here they initiate melanogenesis and further maturation into stage III melanosomes, characterised by melanin deposition onto internal striations. Finally, stage IV melanosomes are fully mature melanised organelles. Epidermal melanocytes and surrounding keratinocytes form a symbiotic functional relationship, termed the epidermal‐melanin unit that consists of around 36 keratinocytes to each melanocyte [97,98]. The precise process of melanosomal transfer from melanocyte dendrites into keratinocytes is not clear, but possible mechanisms include: cytophagocytosis of dendrite tips by keratinocytes; exocytosis of melanin from melanocytes followed by their uptake by keratinocytes via phagocytosis; transfer via membrane‐bound vesicles; or direct fusion of plasma membranes of the melanocyte and associated keratinocytes (Figure 1.1.7.) [99]. Once transferred from the melanocyte, melanin accumulates above the nuclei of keratinocytes, where it serves to protect mitotic keratinocytes from the ionising effects of UV irradiation [100]. This is achieved by scattering UV radiation or absorbing it and converting it into heat, or by absorbing DNA damage‐causing free radicals generated in the cytoplasm (reviewed in [101]. In the event of extreme or repeated exposure to UV irradiation, increased synthesis of melanin is evident by “tanning”. Complex signalling networks between keratinocytes, melanocytes and skin fibroblasts maintain skin homeostasis, and in the case of increased UV exposure result in an increase in melanogenesis as well as in the number and dendricity of melanocytes [20,102,103]. Melanocyte signalling pathways A very comple...
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This document was uploaded on 03/06/2014 for the course CHEMISTRY 12 at National University of Singapore.

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