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. Author manuscript; available in PMC: 2014 May 1.
Published in final edited form as: Pigment Cell Melanoma Res. 2013 Feb 19;26(3):300–315. doi: 10.1111/pcmr.12067

Figure 5. PMEL trafficking to stage I and II melanosomes.

Figure 5

a, schematic of the trafficking pathway for PMEL from its site of synthesis in the endoplasmic reticulum (ER) through the Golgi and trans Golgi network (TGN) and the plasma membrane, ultimately to stage I and II melanosomes. Red arrows depict trafficking steps, and PMEL domains are colored as in Figure 4. The predominant processed PMEL isoform is indicated within each organelle. The blue arrow indicated PMEL CTF trafficking to lysosomes. Also shown are the clathrin-associated adaptors AP-2 – which facilitates PMEL endocytosis from the plasma membrane – and AP-1 and AP-3 – which associate with separate domains of early endosomes/ stage I melanosomes. Tyrosinase and Tyrp1 are delivered to maturing stage III and IV melanosomes via transport carriers that emerge from these domains. b, enlarged schematic of stage I melanosomes emphasizing processing of PMEL by S2P and subsequent ESCRT-independent sorting of (i) PMEL-Mα to ILVs, from which fibrils emanate, and (ii) CTF to an ESCRT- and γ-secretase dependent degradation pathway in lysosomes.