Junctions tighten myelin sheaths
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《细胞学杂志》
Tight junction-like structures run along myelin sheaths in both the central and peripheral nervous systems (CNS and PNS), but have only been functionally characterized in the CNS. Miyamoto et al. (page 527) find evidence that these structures work as true tight junctions to seal off the myelin sheath and are required for proper neural conductance in the Schwann cells of the PNS.Claudin proteins are major cell adhesion molecules in tight junctions. Mutations in claudin-11 compromise the CNS, but leave the PNS untouched, begging the question as to whether the morphologically similar structures in the PNS act as tight junctions and if so whether a claudin family member is involved
Miyamoto et al. went looking for a claudin family member expressed in the PNS. Claudin-19 fit the bill. Mice lacking functional claudin-19 showed behavioral and morphological abnormalities suggestive of peripheral nerve damage and disruption of the tight junction-like structures. Recordings of compound action potentials showed two currents, one fast and one slow. This change in conductance properties indicated that, without claudin-19, the myelin sheath of Schwann cell appeared to be inadequately sealed from the environment. Thus the mutation may have interfered with normal saltatory travel of neural currents.
The dependence on tight junctions may be greater in thinner myelinated axons than in thicker ones because the thinner axons lack the bulk that would compensate for improperly sealed wrappings. The team is continuing to follow the now two-year-old mice to see if a lack of proper tight junctions induces demyelination later in life.(Claudin-19 (green) helps form tight junc)
Miyamoto et al. went looking for a claudin family member expressed in the PNS. Claudin-19 fit the bill. Mice lacking functional claudin-19 showed behavioral and morphological abnormalities suggestive of peripheral nerve damage and disruption of the tight junction-like structures. Recordings of compound action potentials showed two currents, one fast and one slow. This change in conductance properties indicated that, without claudin-19, the myelin sheath of Schwann cell appeared to be inadequately sealed from the environment. Thus the mutation may have interfered with normal saltatory travel of neural currents.
The dependence on tight junctions may be greater in thinner myelinated axons than in thicker ones because the thinner axons lack the bulk that would compensate for improperly sealed wrappings. The team is continuing to follow the now two-year-old mice to see if a lack of proper tight junctions induces demyelination later in life.(Claudin-19 (green) helps form tight junc)