
Melanophilin (Mlph) mediates the association of myosin-5a (Myo5a) with melanosome through three distinct interactions: the exon-F/EFBD interaction, the exon-G/ABD interaction, and the GTD/GTBM interaction. These three interactions act synergistically to enable the tight binding of Myo5a to Mlph and the subsequent transport of melanosomes.


coremsg

Transport and localization of melanosome at the periphery region of melanocyte are depended on myosin-5a (Myo5a), which associates with melanosome by interacting with its adaptor protein melanophilin (Mlph). Mlph contains four functional regions, including Rab27a-binding domain, Myo5a GTD-binding motif (GTBM), Myo5a exon F-binding domain (EFBD), and actin-binding domain (ABD). The association of Myo5a with Mlph is known to be mediated by two specific interactions: the interaction between the exon-F-encoded region of Myo5a and Mlph-EFBD and that between Myo5a-GTD and Mlph-GTBM. Here, we identify a third interaction between Myo5a and Mlph, i.e., the interaction between the exon-G-encoded region of Myo5a and Mlph-ABD. The exon-G/ABD interaction is independent from the exon-F/EFBD interaction and is required for the association of Myo5a with melanosome. Moreover, we demonstrate that Mlph-ABD interacts with either the exon-G or actin filament, but cannot interact with both of them simultaneously. Based on above findings, we propose a new model for the Mlph-mediated Myo5a transportation of melanosomes.

### Competing Interest Statement

The authors have declared no competing interest.

Melanophilin mediates the association of myosin-5a with melanosome via three distinct interactions

melanophilin-mediates-three-distinct-interactions-with-myosin-5a-to-facilitate-melanosome-transport-in-melanocytes


Melanophilin Mediates Three Distinct Interactions with Myosin-5a to Facilitate Melanosome Transport in Melanocytes
