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Removal of the negatively charged glycocalyx becomes the limiting factor in such transition. What is required to initiate this membrane\u2010zipping process? Knocking\u2010out the Lipocalin Apolipoprotein D (ApoD), essential for lysosomal functional integrity in glial cells, results in a specific defect in myelin extracellular leaflet compaction in peripheral and central nervous system, which results in reduced conduction velocity and suboptimal behavioral outputs: motor learning is compromised. Myelination initiation, growth, intracellular leaflet compaction, myelin thickness or internodal length remain unaltered. Lack of ApoD specifically modifies Plp and P0 protein expression, but not Mbp or Mag. Late in myelin maturation period, ApoD affects lipogenic and growth\u2010related, but not stress\u2010responsive, signaling pathways. Without ApoD, the sialylated glycocalyx is maintained and ganglioside content remains high. In peripheral nervous system, Neu3 membrane sialidase and lysosomal Neu1 are coordinately expressed with ApoD in subsets of Schwann cells. ApoD\u2010KO myelin becomes depleted of Neu3 and enriched in Fyn, a kinase with pivotal roles in transducing axon\u2010derived signals into myelin properties. In the absence of ApoD, partial permeabilization of lysosomes alters Neu1 location as well. Exogenous ApoD rescues ApoD\u2010KO hypersialylated glycocalyx in astrocytes, demonstrating that ApoD is necessary and sufficient to control glycocalyx composition in glial cells. By ensuring lysosomal functional integrity and adequate subcellular location of effector and regulatory proteins, ApoD guarantees the glycolipid recycling and glycocalyx removal required to complete myelin compaction.<\/jats:p>","DOI":"10.1002\/glia.23274","type":"journal-article","created":{"date-parts":[[2017,12,9]],"date-time":"2017-12-09T11:58:43Z","timestamp":1512820723000},"page":"670-687","source":"Crossref","is-referenced-by-count":31,"title":["<scp>M<\/scp>yelin extracellular leaflet compaction requires apolipoprotein <scp>D<\/scp> membrane management to optimize lysosomal\u2010dependent recycling and glycocalyx removal"],"prefix":"10.1002","volume":"66","author":[{"given":"Nadia","family":"Garc\u00eda\u2010Mateo","sequence":"first","affiliation":[{"name":"Instituto de Biolog\u00eda y Gen\u00e9tica Molecular\u2010Departamento de Bioqu\u00edmica y Biolog\u00eda Molecular y Fisiolog\u00eda, Universidad de Valladolid\u2010CSIC Valladolid 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