A Novel Role for Embigin to Promote Sprouting of Motor Nerve Terminals at the Neuromuscular Junction

Abstract

Adult skeletal muscle accepts ectopic innervation by foreign motor axons only after section of its own nerve, suggesting that the formation of new neuromuscular junctions is promoted by muscle denervation. With the aim to identify new proteins involved in neuromuscular junction formation we performed an mRNA differential display on innervated versus denervated adult rat muscles. We identified transcripts encoding embigin, a transmembrane protein of the immunoglobulin superfamily (IgSF) class of cell adhesion molecules to be strongly regulated by the state of innervation. In innervated muscle it is preferentially localized to neuromuscular junctions. Forced overexpression in innervated muscle of a full-length embigin transgene, but not of an embigin fragment lacking the intracellular domain, promotes nerve terminal sprouting and the formation of additional acetylcholine receptor clusters at synaptic sites without affecting terminal Schwann cell number or morphology, and it delays the retraction of terminal sprouts following re-innervation of denervated endplates. Conversely, knockdown of embigin by RNA interference in wild-type muscle accelerates terminal sprout retraction, both by itself and synergistically with deletion of neural cell adhesion molecule. These findings indicate that embigin enhances neural cell adhesion molecule-dependent neuromuscular adhesion and thereby modulates neuromuscular junction formation and plasticity.

Comparison of carnivore, omnivore, and herbivore mammalian genomes with a new leopard assembly

“…2b), congruent with the suggestion that adaptive molecular convergence linked to phenotypic convergence is rare [49]. Interestingly, EMB , which was predicted to be functionally altered in the three carnivore clades, is known to play a role in the outgrowth of motor neurons and in the formation of neuromuscular junctions [50]. We confirmed that the AAC in EMB gene is also conserved in the domestic ferret.…”

CD147 subunit of lactate/H+symporters MCT1 and hypoxia-inducible MCT4 is critical for energetics and growth of glycolytic tumors

“…Embigin is a paralog of Basigin that, with the exception of the conserved transmembrane segment, shares <30% homology. Furthermore, unlike Basigin, Embigin has not been reported as a protumoral protein and does not mediate cell aggregation by homophilic interactions, suggesting different modes of function for the two (35). Interestingly, Embigin maintained expression of MCTs in basigin-knockout cells (compare Fig.…”

Proximity-Based Differential Single-Cell Analysis of the Niche to Identify Stem/Progenitor Cell Regulators

“…Embigin is thought to enhance integrin-dependent cell substrate adhesion and was also shown to promote neuromuscular synapse formation (Lain et al, 2009). Embigin is widely expressed within the hematopoietic system, including primitive hematopoietic cells (Pridans et al, 2008), but its function remains obscure.…”