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Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
Published on: June 7, 2019
Pmel17 initiates premelanosome morphogenesis within multivesicular bodies
J F Berson1, D C Harper, D Tenza
1Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Molecular Biology of the Cell
|November 6, 2001
Summary
The melanocyte glycoprotein Pmel17 is cleaved into two subunits, M alpha and M beta, and drives the formation of premelanosomal striations. This suggests Pmel17
Area of Science:
- Cell Biology
- Biochemistry
- Melanogenesis Research
Background:
- Melanosomes are organelles for melanin synthesis and storage.
- Pmel17 glycoprotein is found in premelanosome lumens and associates with striations.
- Pmel17 is synthesized as an integral membrane protein, raising questions about its linkage to premelanosomes.
Purpose of the Study:
- To investigate the posttranslational processing of human Pmel17.
- To clarify the physical linkage of Pmel17 to premelanosomes.
- To determine Pmel17's role in premelanosome biogenesis.
Main Methods:
- Analysis of posttranslational processing of human Pmel17.
- Studying Pmel17 in pigmented and transfected nonpigmented cells.
- Cellular and subcellular localization studies.
Main Results:
- Pmel17 is cleaved into disulfide-linked lumenal (M alpha) and membrane (M beta) subunits in a post-Golgi compartment.
- The M alpha subunit remains membrane-bound, associated with M beta.
- Overexpression of Pmel17 in nonpigmented cells induced structures resembling premelanosomal striations within multivesicular bodies.
Conclusions:
- Pmel17 processing involves cleavage into associated lumenal and membrane subunits.
- Pmel17 is sufficient to induce striation formation within multivesicular bodies.
- Pmel17 plays a direct role in the biogenesis of premelanosomes.
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