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

Abstract

Anterograde 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 behavior 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.

Large Rab GTPase Rab44 regulates microtubule-dependent retrograde melanosome transport in melanocytes

“…In contrast to the single machinery responsible for actin-based melanosome transport, both the anterograde and the retrograde melanosome transport on microtubules appear to be controlled by several distinct machineries ( 16 , 17 , 18 , 19 , 20 ), but their precise regulatory mechanisms are poorly understood. Two distinct machineries of retrograde melanosome transport have previously been reported.…”