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Integrin-linked kinase regulates melanosome trafficking and melanin transfer in melanocytes
Molecular Biology of the Cell
  • Melissa Crawford, Western University
  • Nancy Liu, Western University
  • Elahe Mahdipour, Western University
  • Kevin Barr, Western University
  • Bryan Heit, Robarts Research Institute
  • Lina Dagnino, Western University
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Melanosomes are melanin-containing organelles that provide pigmentation and protection from solar UV radiation to the skin. In melanocytes, melanosomes mature and traffic to dendritic tips, where they are transferred to adjacent epidermal keratinocytes through pathways that involve microtubule networks and the actin cytoskeleton. However, the role of scaffold proteins in these processes is poorly understood. Integrin-linked kinase (ILK) is a scaffold protein that regulates microtubule stability and F-actin dynamics. Here we show that ILK is necessary for normal trafficking of melanosomes along microtubule tracks. In the absence of ILK, immature melanosomes are not retained in perinuclear regions, and mature melanosome trafficking along microtubule tracks is impaired. These deficits can be attenuated by microtubule stabilization. Microtubules are also necessary for the formation of dendrites in melanocytes, and Ilk inactivation reduces melanocyte dendricity. Activation of glycogen synthase kinase-3 (GSK-3) interferes with microtubule assembly. Significantly, inhibition of GSK-3 activity or exogenous expression of the GSK-3 substrate collapsin response mediator protein 2 (CRMP2) in ILK-deficient melanocytes restored dendricity. ILK is also required for normal melanin transfer, and GSK-3 inhibition in melanocytes partially restored melanin transfer to neighboring keratinocytes. Thus, our work shows that ILK is a central modulator of melanosome movements in primary epidermal melanocytes and identifies ILK and GSK-3 as important modulators of melanin transfer to keratinocytes, a key process for epidermal UV photoprotection.

Citation Information
Melissa Crawford, Nancy Liu, Elahe Mahdipour, Kevin Barr, et al.. "Integrin-linked kinase regulates melanosome trafficking and melanin transfer in melanocytes" Molecular Biology of the Cell Vol. 31 Iss. 8 (2020) p. 768 - 781
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