Mammalian Functional Amyloid - The Functional Fold: Amyloid Structures in Nature - page 150

Figure 9.1 Pmel17 trafficking and function in melanin biosynthesis

and melanosome biogenesis. (a) Pmel17 is synthesized as
a transmembrane protein in the ER (i), it is trafficked first
to the Golgi (ii), and finally to the melanosome. Proprotein
convertase (PC) cleavage in a post-Golgi compartment creates
a lumenal fragment, M

α

, and a transmembrane fragment, Mβ.

M

α

remains disulphide-bonded to Mβ to prohibit aberrant M

α

amyloidogenesis (iii). Degradation of Mβ releases M

α

from the

α

membrane (iv), enabling M to form amyloid fibres within

the melanosome organelle (v). M

α

amyloid fibres orchestrate
the synthesis of melanin from tyrosine-derived reactive
indolequinones and protect the melanocyte from melanin-
associated toxicity (vi). (b) Electron micrograph depicting
the four-stage process of melanosome maturation. Stage I:
melanosomes are vesicles of endosomal origin. Stage II: M

α

amyloid fibres form within the nascent melanosome. Stage III:
melanin appears along M

α

fibres. Stage IV: melanin occludes

the M fibre structure in melanosomes. Part (a) and figure

legend reproduced with permission from Elsevier.

α

5

Electron
micrograph was generated by Ilse Hurbain and Graça Raposo.