PMID- 23621612
OWN - NLM
STAT- MEDLINE
DCOM- 20130911
LR  - 20220129
IS  - 1742-4658 (Electronic)
IS  - 1742-464X (Print)
IS  - 1742-464X (Linking)
VI  - 280
IP  - 14
DP  - 2013 Jul
TI  - Endosomal trafficking of the receptor tyrosine kinase MuSK proceeds via 
      clathrin-dependent pathways, Arf6 and actin.
PG  - 3281-97
LID - 10.1111/febs.12309 [doi]
AB  - Muscle-specific kinase (MuSK), a receptor tyrosine kinase, is the key player 
      during the formation of the neuromuscular junction. Signal transduction events 
      downstream of MuSK activation induce both pre- and postsynaptic differentiation, 
      which, most prominently, includes the clustering of acetylcholine receptors at 
      synaptic sites. More recently, regulated MuSK endocytosis and degradation have 
      been implicated as crucial events for MuSK signalling activity, implicating a 
      cross-talk between signalling and endocytosis. In the present study, we use a 
      live imaging approach to study MuSK endocytosis. We find that MuSK is 
      internalized via a clathrin-, dynamin-dependent pathway. MuSK is transported to 
      Rab7-positive endosomes for degradation and recycled via Rab4- and Rab11-positive 
      vesicles. MuSK activation by Dok7 mildly affects the localization of MuSK on the 
      cell surface but has no effect on the rate of MuSK internalization. 
      Interestingly, MuSK colocalizes with actin and Arf6 at the cell surface and 
      during endosomal trafficking. Disruption of the actin cytoskeleton or the proper 
      function of Arf6 concentrates MuSK in cell protrusions. Moreover, inhibition of 
      Arf6 or cytoskeletal rearrangements impairs acetylcholine receptor clustering and 
      phosphorylation. These results suggest that MuSK uses both classical and 
      nonclassical endosomal pathways that involve a variety of different components of 
      the endosomal machinery.
CI  - (c) 2013 The Authors. FEBS Journal published by John Wiley & Sons Ltd on behalf of 
      FEBS.
FAU - Luiskandl, Susan
AU  - Luiskandl S
AD  - Center for Brain Research, Medical University of Vienna, Vienna, Austria.
FAU - Woller, Barbara
AU  - Woller B
FAU - Schlauf, Marlies
AU  - Schlauf M
FAU - Schmid, Johannes A
AU  - Schmid JA
FAU - Herbst, Ruth
AU  - Herbst R
LA  - eng
GR  - P 19223/FWF_/Austrian Science Fund FWF/Austria
GR  - P 21667/FWF_/Austrian Science Fund FWF/Austria
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130523
PL  - England
TA  - FEBS J
JT  - The FEBS journal
JID - 101229646
RN  - 0 (ADP-Ribosylation Factor 6)
RN  - 0 (Actins)
RN  - 0 (Agrin)
RN  - 0 (Clathrin)
RN  - 0 (Dok-7 protein, mouse)
RN  - 0 (Muscle Proteins)
RN  - 0 (Receptors, Cholinergic)
RN  - 0 (rab7 GTP-Binding Proteins)
RN  - 0 (rab7 GTP-binding proteins, mouse)
RN  - EC 2.7.10.1 (MuSK protein, mouse)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - EC 3.6.1.- (rab11 protein)
RN  - EC 3.6.5.2 (ADP-Ribosylation Factors)
RN  - EC 3.6.5.2 (Arf6 protein, mouse)
RN  - EC 3.6.5.2 (rab GTP-Binding Proteins)
RN  - EC 3.6.5.2 (rab4 GTP-Binding Proteins)
RN  - EC 3.6.5.5 (Dynamins)
SB  - IM
MH  - ADP-Ribosylation Factor 6
MH  - ADP-Ribosylation Factors/*metabolism
MH  - Actins/*metabolism
MH  - Agrin/metabolism
MH  - Animals
MH  - COS Cells
MH  - Chlorocebus aethiops
MH  - Clathrin/*metabolism
MH  - Cytoskeleton/metabolism
MH  - Dynamins/metabolism
MH  - *Endocytosis
MH  - Endosomes/enzymology
MH  - Mice
MH  - Muscle Proteins/metabolism
MH  - Protein Transport
MH  - Proteolysis
MH  - Receptor Protein-Tyrosine Kinases/*metabolism
MH  - Receptors, Cholinergic/metabolism
MH  - rab GTP-Binding Proteins/metabolism
MH  - rab4 GTP-Binding Proteins/metabolism
MH  - rab7 GTP-Binding Proteins
PMC - PMC3806275
OTO - NOTNLM
OT  - Arf6
OT  - MuSK
OT  - clathrin-independent endocytosis
OT  - endocytosis
OT  - receptor tyrosine kinase
EDAT- 2013/04/30 06:00
MHDA- 2013/09/12 06:00
CRDT- 2013/04/30 06:00
PHST- 2012/12/23 00:00 [received]
PHST- 2013/04/12 00:00 [revised]
PHST- 2013/04/19 00:00 [accepted]
PHST- 2013/04/30 06:00 [entrez]
PHST- 2013/04/30 06:00 [pubmed]
PHST- 2013/09/12 06:00 [medline]
AID - 10.1111/febs.12309 [doi]
PST - ppublish
SO  - FEBS J. 2013 Jul;280(14):3281-97. doi: 10.1111/febs.12309. Epub 2013 May 23.