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Updated: May 30, 2025

Laser Microdissection-Based Protocol for the LC-MS/MS Analysis of the Proteomic Profile of Neuromelanin Granules
Published on: December 16, 2021
Keratin intermediate filaments mechanically position melanin pigments for genome photoprotection
Silvia Benito-Martínez1, Laura Salavessa1,2, Anne-Sophie Macé3
1Institut Curie, PSL Research University, CNRS, UMR144, Structure and Membrane Compartments, 75005 Paris, France.
Abstract:
Melanin pigments block genotoxic agents by positioning on the sun-exposed side of human skin keratinocytes' nucleus. How this position is regulated and its role in genome photoprotection remains unknown. By developing a model of human keratinocytes internalizing extracellular melanin into pigment organelles, we show that keratin 5/14 intermediate filaments mechanically control the 3D perinuclear position of pigments, shielding DNA from photodamage. Imaging and microrheology in human disease-related model identify structural keratin cages surrounding pigment organelles to stiffen their microenvironment and maintain their 3D position. Optimum pigment spatialization is required for DNA photoprotection and rely on the interplay between intermediate filaments and microtubules bridged by plectin cytolinkers. Thus, the mechanically-driven proximity of pigment organelles to the nucleus is a key photoprotective parameter. Uncovering how human skin counteracts solar radiation by positioning the melanin microparasol next to the genome anticipates that dynamic spatialization of organelles is a physiological UV stress response.
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