PMID- 35370548
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231108
IS  - 1662-5099 (Print)
IS  - 1662-5099 (Electronic)
IS  - 1662-5099 (Linking)
VI  - 15
DP  - 2022
TI  - Internalization of Muscle-Specific Kinase Is Increased by Agrin and Independent 
      of Kinase-Activity, Lrp4 and Dynamin.
PG  - 780659
LID - 10.3389/fnmol.2022.780659 [doi]
LID - 780659
AB  - Muscle-specific kinase (MuSK) is a receptor tyrosine kinase absolutely required 
      for neuromuscular junction formation. MuSK is activated by binding of motor 
      neuron-derived Agrin to low-density lipoprotein receptor related protein 4 
      (Lrp4), which forms a complex with MuSK. MuSK activation and downstream signaling 
      are critical events during the development of the neuromuscular junction. 
      Receptor tyrosine kinases are commonly internalized upon ligand binding and 
      crosstalk between endocytosis and signaling has been implicated. To extend our 
      knowledge about endocytosis of synaptic proteins and its role during postsynaptic 
      differentiation at the neuromuscular junction, we studied the stability and 
      internalization of Lrp4, MuSK and acetylcholine receptors (AChRs) in response to 
      Agrin. We provide evidence that MuSK but not Lrp4 internalization is increased by 
      Agrin stimulation. MuSK kinase-activity is not sufficient to induce MuSK 
      internalization and the absence of Lrp4 has no effect on MuSK endocytosis. 
      Moreover, MuSK internalization and signaling are unaffected by the inhibition of 
      Dynamin suggesting that MuSK endocytosis uses a non-conventional pathway and is 
      not required for MuSK-dependent downstream signaling.
CI  - Copyright (c) 2022 Gemza, Barresi, Proemer, Hatami, Lazaridis and Herbst.
FAU - Gemza, Anna
AU  - Gemza A
AD  - Center for Pathophysiology, Infectiology and Immunology, Medical University of 
      Vienna, Vienna, Austria.
FAU - Barresi, Cinzia
AU  - Barresi C
AD  - Center for Pathophysiology, Infectiology and Immunology, Medical University of 
      Vienna, Vienna, Austria.
FAU - Proemer, Jakob
AU  - Proemer J
AD  - Center for Pathophysiology, Infectiology and Immunology, Medical University of 
      Vienna, Vienna, Austria.
FAU - Hatami, Jasmin
AU  - Hatami J
AD  - Center for Pathophysiology, Infectiology and Immunology, Medical University of 
      Vienna, Vienna, Austria.
FAU - Lazaridis, Margarita
AU  - Lazaridis M
AD  - Center for Pathophysiology, Infectiology and Immunology, Medical University of 
      Vienna, Vienna, Austria.
FAU - Herbst, Ruth
AU  - Herbst R
AD  - Center for Pathophysiology, Infectiology and Immunology, Medical University of 
      Vienna, Vienna, Austria.
LA  - eng
GR  - DOC 33/FWF_/Austrian Science Fund FWF/Austria
GR  - P 28485/FWF_/Austrian Science Fund FWF/Austria
GR  - P 31199/FWF_/Austrian Science Fund FWF/Austria
PT  - Journal Article
DEP - 20220315
PL  - Switzerland
TA  - Front Mol Neurosci
JT  - Frontiers in molecular neuroscience
JID - 101477914
PMC - PMC8965242
OTO - NOTNLM
OT  - MuSK
OT  - endocytosis
OT  - neuromuscular junction
OT  - receptor tyrosine kinase
OT  - signal transduction
OT  - skeletal muscle
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/04/05 06:00
MHDA- 2022/04/05 06:01
PMCR- 2022/01/01
CRDT- 2022/04/04 05:27
PHST- 2021/09/21 00:00 [received]
PHST- 2022/02/21 00:00 [accepted]
PHST- 2022/04/04 05:27 [entrez]
PHST- 2022/04/05 06:00 [pubmed]
PHST- 2022/04/05 06:01 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fnmol.2022.780659 [doi]
PST - epublish
SO  - Front Mol Neurosci. 2022 Mar 15;15:780659. doi: 10.3389/fnmol.2022.780659. 
      eCollection 2022.