Identity, developmental restriction and reactivity of extralaminar cells capping mammalian neuromuscular junctions

Abstract

Neuromuscular junctions (NMJs) are normally thought to comprise three major cell types: skeletal muscle fibres, motor neuron terminals and perisynaptic terminal Schwann cells. Here we studied a fourth population of junctional cells in mice and rats, revealed using a novel cytoskeletal antibody (2166). These cells lie outside the synaptic basal lamina but form caps over NMJs during postnatal development. NMJ-capping cells also bound rPH, HM-24, CD34 antibodies and cholera toxin B subunit. Bromodeoxyuridine incorporation indicated activation, proliferation and spread of NMJ-capping cells following denervation in adults, in advance of terminal Schwann cell sprouting. The NMJ-capping cell reaction coincided with expression of tenascin-C but was independent of this molecule because capping cells also dispersed after denervation in tenascin-C-null mutant mice. NMJ-capping cells also dispersed after local paralysis with botulinum toxin and in atrophic muscles of transgenic R6/2 mice. We conclude that NMJ-capping cells (proposed name `kranocytes') represent a neglected, canonical cellular constituent of neuromuscular junctions where they could play a permissive role in synaptic regeneration.

The neuropathic potential of anti-GM1 autoantibodies is regulated by the local glycolipid environment in mice

“…levels, staining was also seen elsewhere, including connective tissue and blood vessels; thus, CTB staining over other GM1-bearing structures is also seen in the upper region of Figure 2A (left panel). DG2 ( Figure 2A, middle panel) showed a staining pattern similar to that of CTB, with particularly pronounced staining in this image of the parajunctional fibroblast, an extralaminar cell that caps the NMJ and also bears the GM1 ligand (32). GalNAcT -/-nerve terminals and other structures were not stained under these conditions, as expected (data not shown).…”

Review: Neuromuscular synaptic vulnerability in motor neurone disease: amyotrophic lateral sclerosis and spinal muscular atrophy

“…The post-synaptic muscle fibre is shown in yellow, with characteristic postsynaptic folds and clustering of acetylcholine receptors (AChRs; red). Terminal Schwann cells (TSC) are shown in blue and two NMJ-capping cells (kranocytes; see [65]) are shown in magenta. (B) Schematic diagram illustrating the normal innervation pattern of three muscle fibres (yellow) in an adult mammalian muscle.…”

“…Further work examining the role of heterogeneous glial cell populations in ALS is therefore required. For example, it would be interesting to know whether nonmyelinating terminal Schwann cells and their neighbouring NMJ-capping cells ('kranocytes' [65]) specifically contribute to ALS pathogenesis and early vulnerability of NMJs. This may be particularly important given the emerging role for glial/synaptic interactions in synaptic homeostasis at the NMJ [66,67].…”

Perisynaptic Schwann Cells at the Neuromuscular Synapse: Adaptable, Multitasking Glial Cells

“…It has been suggested that the PSC-associated extracellular matrix may play a role in guiding nerve terminal sprouts at the frog NMJ (Chen and Ko 1994;Ko and Chen 1996; see below). Interestingly, fibroblast-like cells (kranocytes) capping the NMJ have also been shown (Connor and McMahan 1987;Court et al 2008).…”