• Prof. Elior Peles, Weizmann Institute of Science
    Weizmann Institute of Science
  • Title: “Differential subcellular distribution of cell adhesion molecules in neurons guides myelin targeting”
  • Host researcher : Daniela Marazziti

 


Abstract: Myelin forms preferentially around axons while avoiding neuronal cell bodies and dendrites, but the underlying basis of such subcellular targeting is still unknown. Myelination in the central nervous system involves complex intercellular contacts between oligodendrocytes and their underlying axons. Oligodendrocyte-axon contact is mediated by the binding of glial cell adhesion molecules 4 and 1 (Cadm4 and Cadm1) to Cadm3 and Cadm2 present in axons. I will discuss how neuronal Cadms control the avoidance of oligodendrocytes from wrapping around neuronal cell bodies and dendrites. Proteomic analysis of cultured hippocampal neurons revealed the presence of all four Cadm proteins. Using endogenous genomic tagging, we found that Cadm4 and Cadm1 are restricted to the somatodendritic compartment in motor neurons, whereas Cadm3 and Cadm2 are present in all neuronal compartments, including the axon.

Nevertheless, despite the presence of Cadm3 and Cadm2 in cell bodies and dendrites, a soluble Cadm4 extracellular domain (Cadm4-FC) could only bind to axons. This was attributed to the presence of Cadm4 in the somatodendritic compartment. Neuronal deletion of both Cadm4 and Cadm1, or increased expression of Cadm3 in the neuronal soma and dendrites, enabled the binding of Cadm4-Fc to all neuronal compartments and led to somatodendritic ensheathment by oligodendrocytes. Further supporting an inhibitory role for neuronal Cadm4, we show that axonal expression of Cadm4 reduced Cadm4-Fc binding and myelination. Our results demonstrate that, at the neuronal cell bodies and dendrites Cadm4 and Cadm1 act as a local inhibitory signal for myelination. They further reveal that the differential subcellular distribution of Cadm family members in neurons contributes to the preferential targeting of oligodendrocytes to axons.