Related Experiment Video

Updated: Sep 28, 2025

Methods to Study Mrp4-containing Macromolecular Complexes in the Regulation of Fibroblast Migration
10:43

Methods to Study Mrp4-containing Macromolecular Complexes in the Regulation of Fibroblast Migration

Published on: May 19, 2016

6.8K

Internalization of Muscle-Specific Kinase Is Increased by Agrin and Independent of Kinase-Activity, Lrp4 and Dynamin

Anna Gemza1, Cinzia Barresi1, Jakob Proemer1

  • 1Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.

Frontiers in Molecular Neuroscience
|April 4, 2022
PubMed

Insights

Agrin stimulation increases Muscle-specific kinase (MuSK) internalization, but not Low-density lipoprotein receptor related protein 4 (Lrp4). MuSK endocytosis occurs via a non-conventional pathway and is not essential for downstream signaling during neuromuscular junction development.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Molecular Biology

Background:

  • Muscle-specific kinase (MuSK) is crucial for neuromuscular junction (NMJ) formation.
  • MuSK activation involves Agrin binding to Low-density lipoprotein receptor related protein 4 (Lrp4).
  • Receptor tyrosine kinase endocytosis is linked to signaling, but its role at the NMJ is unclear.

Purpose of the Study:

  • To investigate the endocytosis of Lrp4, MuSK, and acetylcholine receptors (AChRs) upon Agrin stimulation.
  • To determine the role of MuSK kinase activity and Lrp4 in MuSK internalization.
  • To elucidate the endocytic pathway of MuSK and its necessity for downstream signaling.

Main Methods:

  • Studied the stability and internalization of Lrp4, MuSK, and AChRs in response to Agrin.
  • Assessed the effect of MuSK kinase activity and Lrp4 absence on MuSK internalization.
  • Investigated MuSK endocytosis and signaling upon Dynamin inhibition.

Main Results:

  • Agrin stimulation enhanced MuSK internalization, but not Lrp4 internalization.
  • MuSK kinase activity alone did not induce MuSK internalization; Lrp4 absence had no effect.
  • MuSK endocytosis and signaling were unaffected by Dynamin inhibition, suggesting a non-conventional pathway.

Conclusions:

  • MuSK, but not Lrp4, undergoes Agrin-induced endocytosis.
  • MuSK internalization is independent of its kinase activity and Lrp4.
  • MuSK endocytosis utilizes a non-conventional pathway and is dispensable for downstream signaling at the NMJ.
Keywords:
MuSKendocytosisneuromuscular junctionreceptor tyrosine kinasesignal transductionskeletal muscle

More Related Videos

Assaying the Kinase Activity of LRRK2 in vitro06:09

Assaying the Kinase Activity of LRRK2 in vitro

Published on: January 18, 2012

22.7K
Characterization at the Molecular Level using Robust Biochemical Approaches of a New Kinase Protein11:23

Characterization at the Molecular Level using Robust Biochemical Approaches of a New Kinase Protein

Published on: June 30, 2019

6.3K

Related Concept Videos

PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
4.1K
Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
2.9K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
6.3K
Generation of Straight or Branched Actin Filaments01:14

Generation of Straight or Branched Actin Filaments

The straight or branched structure formation of actin filaments is controlled by nucleating proteins such as the formins and Arp2/3 complex. Formin-mediated assembly results in straight filaments, whereas Arp2/3 protein complex-mediated assembly results in branched actin filaments.
Arp2/3 Complex
Arp2/3 complex is a seven-subunit complex consisting of two proteins similar to actin- Arp2 and Arp3, and five other subunits that help keep Arp2 and Arp3 inactive. When required, the complex is...
3.0K
Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
4.3K
Mechanism of Lamellipodia Formation01:31

Mechanism of Lamellipodia Formation

Cells migrating in response to external stimuli form lamellipodia, which are thin membrane protrusions supported by a mesh of linked, branched, or unbranched actin filaments. These actin filaments interact with myosin motor proteins, creating the dynamic actomyosin complex within the cytoskeleton. Contractility, or the ability to generate contractile stress, is inherent to the actomyosin complex. It helps cells detect the stiffness of the surrounding ECM and exert contractile force for...
2.8K