CD24 is expressed by myofiber synaptic nuclei and regulates synaptic transmission

Proc Natl Acad Sci U S A. 2006 Apr 18;103(16):6374-9. doi: 10.1073/pnas.0601468103. Epub 2006 Apr 10.

Abstract

The genes encoding several synaptic proteins, including acetylcholine receptors, acetylcholinesterase, and the muscle-specific kinase, MuSK, are expressed selectively by a small number of myofiber nuclei positioned near the synaptic site. Genetic analysis of mutant mice suggests that additional genes, expressed selectively by synaptic nuclei, might encode muscle-derived retrograde signals that regulate the differentiation of motor axon terminals. To identify candidate retrograde signals, we used a microarray screen to identify genes that are preferentially expressed in the synaptic region of muscle, and we analyzed one such gene, CD24, further. We show that CD24, which encodes a small, variably and highly glycosylated, glycosylphosphatidylinositol (GPI)-linked protein, is expressed preferentially by myofiber synaptic nuclei in embryonic and adult muscle, and that CD24 expression is restricted to the central region of muscle independent of innervation. Moreover, we show that CD24 has a role in presynaptic differentiation, because synaptic transmission is depressed and fails entirely, in a cyclical manner, after repetitive stimulation of motor axons in CD24 mutant mice. These deficits in synaptic transmission, which are accompanied by aberrant stimulus-dependent uptake of AM1-43 from axons, indicate that CD24 is required for normal presynaptic maturation and function. Because CD24 is also expressed in some neurons, additional experiments will be required to determine whether pre- or postsynaptic CD24 mediates these effects on presynaptic development and function.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD24 Antigen / genetics
  • CD24 Antigen / metabolism*
  • Cell Nucleus / metabolism
  • Male
  • Mice
  • Mice, Mutant Strains
  • Molecular Sequence Data
  • Muscle Fibers, Skeletal / chemistry
  • Muscle Fibers, Skeletal / metabolism*
  • Muscle, Skeletal / chemistry
  • Muscle, Skeletal / innervation
  • Muscle, Skeletal / metabolism
  • Neural Cell Adhesion Molecules / metabolism
  • Neuromuscular Junction / chemistry
  • Neuromuscular Junction / genetics
  • Neuromuscular Junction / metabolism*
  • Oligonucleotide Array Sequence Analysis
  • RNA, Messenger / analysis
  • RNA, Messenger / metabolism
  • Synaptic Transmission* / genetics

Substances

  • CD24 Antigen
  • Neural Cell Adhesion Molecules
  • RNA, Messenger

Associated data

  • RefSeq/NM_009846