Myosin VI and its interacting protein LMTK2 regulate tubule formation and transport to the endocytic recycling compartment

Abstract

Myosin VI is an actin-based retrograde motor protein that plays a crucial role in both endocytic and secretory membrane trafficking pathways. Myosin VI's targeting to and function in these intracellular pathways is mediated by a number of specific binding partners. In this paper we have identified a new myosin-VI-binding partner, lemur tyrosine kinase 2 (LMTK2), which is the first transmembrane protein and kinase that directly binds to myosin VI. LMTK2 binds to the WWY site in the C-terminal myosin VI tail, the same site as the endocytic adaptor protein Dab2. When either myosin VI or LMTK2 is depleted by siRNAs, the transferrin receptor (TfR) is trapped in swollen endosomes and tubule formation in the endocytic recycling pathway is dramatically reduced, showing that both proteins are required for the transport of cargo, such as the TfR, from early endosomes to the endocytic recycling compartment.