Myosin VI and its interacting protein LMTK2 regulate tubule formation and transport to the endocytic recycling compartment.
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.
Chibalina
Margarita V
MV
Cambridge Institute for Medical Research, University of Cambridge, Wellcome Trust/MRC Building, Hills Road, Cambridge, CB2 2XY, UK.
Seaman
Matthew N J
MN
Miller
Christopher C
CC
Kendrick-Jones
John
J
Buss
Folma
F
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D051017:Apoptosis Regulatory Proteins; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D004705:Endocytosis / Q000502:physiology; D011992:Endosomes / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000378:metabolism*; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D021381:Protein Transport; D011990:Receptors, Transferrin / Q000378:metabolism; D014168:Transferrin / Q000378:metabolism; D025521:Tumor Suppressor Proteins
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C102885:DAB2 protein, human; D008565:Membrane Proteins; D011990:Receptors, Transferrin; D014168:Transferrin; D025521:Tumor Suppressor Proteins; C089785:myosin VI; C470798:LMTK2 protein, human; D017346:Protein Serine-Threonine Kinases; D018995:Myosin Heavy Chains