Exp Neurobiol.  2017 Jun;26(3):141-150. 10.5607/en.2017.26.3.141.

The Scaffolding Protein, Grb2-associated Binder-1, in Skeletal Muscles and Terminal Schwann Cells Regulates Postnatal Neuromuscular Synapse Maturation

• Park SY
• Jang SY
• Shin YK
• Jung DK
• Yoon BA
• Kim JK
• Jo YR
• Lee HJ
• Park HT

• KMID: 2383783
• DOI: http://doi.org/10.5607/en.2017.26.3.141

Abstract

The vertebrate neuromuscular junction (NMJ) is considered as a "tripartite synapse" consisting of a motor axon terminal, a muscle endplate, and terminal Schwann cells that envelope the motor axon terminal. The neuregulin 1 (NRG1)-ErbB2 signaling pathway plays an important role in the development of the NMJ. We previously showed that Grb2-associated binder 1 (Gab1), a scaffolding mediator of receptor tyrosine kinase signaling, is required for NRG1-induced peripheral nerve myelination. Here, we determined the role of Gab1 in the development of the NMJ using muscle-specific conditional Gab1 knockout mice. The mutant mice showed delayed postnatal maturation of the NMJ. Furthermore, the selective loss of the gab1 gene in terminal Schwann cells produced delayed synaptic elimination with abnormal morphology of the motor endplate, suggesting that Gab1 in both muscles and terminal Schwann cells is required for proper NMJ development. Gab1 in terminal Schwann cells appeared to regulate the number and process elongation of terminal Schwann cells during synaptic elimination. However, Gab2 knockout mice did not show any defects in the development of the NMJ. Considering the role of Gab1 in postnatal peripheral nerve myelination, our findings suggest that Gab1 is a pleiotropic and important component of NRG1 signals during postnatal development of the peripheral neuromuscular system.

Keyword

Neuregulin-1; Grb2-associated binders (Gab); Terminal Schwann cells; Neuromuscular junction; Synaptic elimination

MeSH Terms

Animals
Mice
Mice, Knockout
Motor Endplate
Muscle, Skeletal*
Muscles
Myelin Sheath
Neuregulin-1
Neuromuscular Junction
Peripheral Nerves
Presynaptic Terminals
Protein-Tyrosine Kinases
Schwann Cells*
Synapses*
Vertebrates
Neuregulin-1
Protein-Tyrosine Kinases