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Endosomal trafficking of the receptor tyrosine kinase MuSK proceeds via clathrin‐dependent pathways, A rf6 and actin
Author(s) -
Luiskandl Susan,
Woller Barbara,
Schlauf Marlies,
Schmid Johannes A.,
Herbst Ruth
Publication year - 2013
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.12309
Subject(s) - microbiology and biotechnology , endosome , endocytosis , internalization , biology , clathrin , actin cytoskeleton , signal transduction , receptor tyrosine kinase , dynamin , acetylcholine receptor , cytoskeleton , receptor , biochemistry , cell , intracellular
Muscle‐specific kinase ( M u SK ), a receptor tyrosine kinase, is the key player during the formation of the neuromuscular junction. Signal transduction events downstream of M u SK activation induce both pre‐ and postsynaptic differentiation, which, most prominently, includes the clustering of acetylcholine receptors at synaptic sites. More recently, regulated M u SK endocytosis and degradation have been implicated as crucial events for M u SK signalling activity, implicating a cross‐talk between signalling and endocytosis. In the present study, we use a live imaging approach to study M u SK endocytosis. We find that M u SK is internalized via a clathrin‐, dynamin‐dependent pathway. Mu SK is transported to Rab7‐positive endosomes for degradation and recycled via Rab4‐ and Rab11‐positive vesicles. Mu SK activation by D ok7 mildly affects the localization of M u SK on the cell surface but has no effect on the rate of M u SK internalization. Interestingly, M u SK colocalizes with actin and Arf6 at the cell surface and during endosomal trafficking. Disruption of the actin cytoskeleton or the proper function of A rf6 concentrates M u SK in cell protrusions. Moreover, inhibition of A rf6 or cytoskeletal rearrangements impairs acetylcholine receptor clustering and phosphorylation. These results suggest that M u SK uses both classical and nonclassical endosomal pathways that involve a variety of different components of the endosomal machinery. Structured digital abstractMuSK and Arf6 colocalize by fluorescence microscopy (View Interaction: 1 , 2 ) MuSK and Rab4 colocalize by fluorescence microscopy ( View interaction ) MuSK and Rab11 colocalize by fluorescence microscopy ( View interaction ) MuSK and Rab7 colocalize by fluorescence microscopy ( View interaction )