Essential Role for Integrin-Linked Kinase in Melanoblast Colonization of the Skin

Integrin-linked kinase regulates melanosome trafficking and melanin transfer in melanocytes

“…In these cultures, 57% and 75% of melanocytes exhibited circularity values ≤0.32 in the absence and presence of SB216763, respectively (Figure 5B). By comparison, the mean circularity value of untreated ILK KO cells was 0.38, significantly higher than that in ILK + melanocytes, in agreement with the recently identified decreased ability of ILK-deficient cells to form dendrites (Crawford et al, 2019). Treatment with SB216763 increased dendricity in ILK KO melanocytes, decreasing mean circularity to 0.26 (Figure 5B).…”

“…This approach allowed us to better visualize Rab7 and Rab9a immunoreactivity in targeted cells, without mTomato-associated fluorescence. In these cells, ILK becomes undetectable 5 d after AdCre transduction (Supplemental Figure 2A; Crawford et al, 2019). In agreement with their reported localization to endosomes and early melanosomes, respectively, Rab9a and Rab7 immunoreactivities were reciprocally exclusive in the majority of vesicles in nontransduced ILK-expressing FIGURE 1: Altered melanosome dynamics in ILK KO melanocytes.…”

“…In the absence of CreER T2 activation, these cells express a membrane-bound form of Tomato fluorescent protein (mTomato) (Crawford et al, 2017). Treatment with 4OHT yields ILK-deficient cells that can be identified readily because they express a membrane-bound form of GFP, although mTomato fluorescence remains detectable in these cells up to 5-7 d after 4OHT administration (Supplemental Figure 1A; Crawford et al, 2019). Under these conditions, the amount of melanin present in ILK KO melanocytes is similar to that in ILK-expressing cells (Supplemental Figure 1B).…”

“…ILK is required for the generation of cell protrusions involved in embryonic melanoblast migration and homing to the skin. In postnatal epidermal melanocytes, ILK also mediates formation and elongation of actin-rich dendrites in response to soluble factors or extracellular matrix substrates, through Rac1-dependent processes (Crawford et al, 2019). Given that dendrite formation and cytoskeletal rearrangements are requisites for optimal melanin transfer, we investigated the role of ILK in modulation of melanosome movements.…”

Rac1, A Potential Target for Tumor Therapy

“…The Rac1 mutant (P29s) melanoma cells can up-regulate the formation of platelet lipoprotein through dendritic actin polymerization (29). When the integrinassociated kinase gene is inactivated in mature melanocytes, motility and dendritic defects occur, which are recovered in the presence of Rac1 (30). Urobilin A (UA), a metabolite of intestinal bacteria, inhibits cell proliferation and migration through destroying the activities of Rac1 and PAK1 (31) (Figure 1).…”