kinesin recruitment by adapter SKIP on melanosomes is dynamically controlled by LC3B phosphorylation

Abstract

AbstractAnterograde melanosome transport is essential for adaptive skin tanning response. However, the molecular components involved, their interplay and regulation by external cues in melanosome transport remain under-explored. Silencing of kinesin motors revealed that several members including the established KIF5B and a novel candidate KIF1B, mediate melanosome movement. The camouflage behaviour of zebrafish embryos induced by incident light or α -MSH requires kif1b, suggesting a conserved melanosome transport machinery across vertebrates. Interestingly, the peri-nuclear melanosome accumulation upon kinesin knockdown is recapitulated by the silencing of autophagy effector MAP1LC3B (LC3B). Pull-down assays identified KIF1B, but not KIF5B, to be the LC3B-associated kinesin. LC3B binds the adapter SKIP via its LIR docking region that is proximal to Thr12 residue, a site for phosphorylation by Protein Kinase A. We demonstrate that phosphorylation of LC3B at Thr12 is stimulated by α-MSH, which potentiates the anterograde melanosome transport. Thereby, our study, identifies a novel kinesin motor KIF1B for melanosome movement and establishes LC3B as the key molecular component that facilitates α-MSH responsive mobilization of melanosomes.Key HighlightsKinesin screen reveals non-redundant use of KIF5B, KIF1B motors for melanosome transportkif1b is required for camouflage response in zebrafish and melanosome movement in mammalsN-terminal region of LC3B interacts with adapter SKIP and couples kinesin KIF1Bα-MSH activates PKA-mediated phosphorylation of LC3B to potentiate anterograde movementSignificanceMelanosomes are lysosome related organelles containing melanin pigment, that are synthesized in melanocytes and transferred to the recipient keratinocytes of skin. This involves long range melanosome movement within melanocytes to reach cell periphery for the transfer to follow. Physiologically, UV protection involves local secretion of melanocyte stimulating hormone (α-MSH) that acts on melanocytes to promote skin tanning response. Herein, we investigate the components involved in this process and establish that the melanosome movement is dynamically controlled by α-MSH through phosphorylation of LC3B. These findings establish the mechanism behind the rapid distribution of melanosomes during tanning response and provide opportunity to intervene for sun protection.