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Joanne F. Berson led a 2001 study of how Pmel17 helps form premelanosomes, the developing compartments in which melanin is deposited. The researchers followed processing and localization of the protein, then expressed it in nonpigmented cells. Expression alone initiated characteristic internal striations within multivesicular bodies.^[ref]

That reconstruction addressed causation more directly than finding Pmel17 beside existing pigment: a normally nonpigmented cell acquired part of the specialized internal architecture after the protein was introduced. It established a role in compartment construction without implying that one protein recreates every step of pigment production.

A multivesicular body is an endosome containing multiple small vesicles within its lumen. These internal vesicles form when regions of the boundary cell membrane bud inward and undergo separation. This reverses the familiar direction of a transport vesicle budding outward into the cytosol.

Membrane topology explains a useful consequence. A cytosol-facing portion of a membrane protein becomes enclosed inside an internal vesicle; subsequent delivery to a lysosome can expose the whole cargo to degradation. Sorting onto an internal vesicle can therefore remove a signalling receptor from the cytosolic machinery that it previously contacted.

A reconstitution experiment added purified ESCRT-III components to large artificial vesicles and observed formation and detachment of inward buds. This demonstrated a direct membrane-separation activity in a simplified system, rather than merely finding the proteins near cellular multivesicular bodies.^[ref]

Pmel17 is a pigment-cell glycoprotein that helps build the internal scaffold of developing melanosomes, the organelles in which melanin is produced and stored. It is synthesized as a membrane protein, but processing produces a large lumen-facing component associated with the characteristic internal striations of immature melanosomes. The scaffold and the pigment deposited on it are different materials.

Joanne F. Berson and colleagues expressed Pmel17 in nonpigmented cells. Electron microscopy revealed striation-like structures inside multivesicular bodies, compartments that normally lack the specialized pigment-cell architecture. Together with localization and processing experiments in pigmented cells, this supported a direct role for Pmel17 in constructing the melanosome interior. It demonstrates how adding a particular protein can reshape a general intracellular compartment into a specialized organelle.^[ref]

A premelanosome is an immature melanosome whose internal architecture is developing before the compartment becomes heavily filled with melanin. In a characteristic maturation sequence, an initially vesicular compartment develops internal striations and then accumulates pigment on the resulting scaffold. “Immature” therefore describes a stage of an organelle's development, rather than a different kind of pigment.

Pmel17 helps construct that scaffold. Joanne F. Berson and colleagues localized processed Pmel17 to internal vesicles and striations of premelanosomes. Expressing the protein in nonpigmented cells also generated striation-like structures in multivesicular bodies.^[ref] Building the scaffold can thus be distinguished experimentally from synthesizing the pigment that later occupies it.