P0Protein Is Required for and Can Induce Formation of Schmidt-Lantermann Incisures in Myelin Internodes

Abstract

Axons in the PNS and CNS are ensheathed by multiple layers of tightly compacted myelin membranes. A series of cytoplasmic channels connect outer and inner margins of PNS, but not CNS, myelin internodes. Membranes of these Schmidt-Lantermann (S-L) incisures contain the myelin-associated glycoprotein (MAG) but not P(0) or proteolipid protein (PLP), the structural proteins of compact PNS (P(0)) and CNS (PLP) myelin. We show here that incisures are present in MAG-null and absent from P(0)-null PNS internodes. To test the possibility that P(0) regulates incisure formation, we replaced PLP with P(0) in CNS myelin. S-L incisures formed in P(0)-CNS myelin internodes. Furthermore, axoplasm ensheathed by 65% of the CNS incisures examined by electron microscopy had focal accumulations of organelles, indicating that these CNS incisures disrupt axonal transport. These data support the hypotheses that P(0) protein is required for and can induce S-L incisures and that P(0)-induced CNS incisures can be detrimental to axonal function.