We have studied the molecular function of proteolipid protein (PLP), the main integral membrane protein of CNS myelin, by generating mice lacking PLP expression. Here, we demonstrate that these PLP-minus mice show no pleiotropism as mice carrying point mutations within the PLP gene. The expression of other myelin genes (myelin basic protein, MBP; myelin associated glycoprotein, MAG; UDP-galacto...

The cellular and subcellular distributions of mRNAs encoding three myelin-specific proteins--myelin basic protein (MBP), proteolipid protein (PLP), and Po protein--were studied in tissue sections of developing rat nervous systems by in situ hybridization. The developmental appearance of these mRNAs closely paralleled the appearance of the proteins they encode as determined by immunocytochemistr...

The velocity of the nerve impulse conduction of vertebrates relies on the myelin sheath, an electrically insulating layer that surrounds axons in both the central and peripheral nervous systems, enabling saltatory conduction of the action potential. Oligodendrocytes are the myelin-producing glial cells in the central nervous system. A deeper understanding of the molecular basis of myelination a...

Myelin proteolipid protein (PLP), the main integral membrane protein in the central nervous system myelin, was labeled at the extracytoplasmic domains with the membrane impermeant reagents pyridoxal 5'-phosphate and tritiated borohydride. Lysine-217, located in the fourth hydrophilic domain of PLP, was found to be the major labeled residue, which defined this domain to be extracytoplasmic in ag...

Myelination of axons in the CNS by oligodendrocytes is a process critical to rapid and efficient impulse conduction. A new role for the myelin proteolipid protein (PLP), the most abundant protein of CNS myelin, has been identified, in studies showing PLP interaction with signaling proteins in oligodendrocytes. In particular, these studies suggest that the PLP protein may be involved in signalin...

Incubation of rat brain myelin with [3H]palmitic acid in the presence of ATP, CoA and MgCl2 or [14C]-palmitoyl-CoA in a cell-free system resulted in the selective labelling of 'PLP' [proteolipid protein; Folch & Lees (1951) J. Biol. Chem. 191, 807-817] and 'DM-20' [Agrawal, Burton, Fishman, Mitchell & Prensky (1972) J. Neurochem. 19, 2083-2089] which, after polyacrylamide-gel electrophoresis in...

During vertebrate brain development, axons are enwrapped by myelin, an insulating membrane produced by oligodendrocytes. Neuron-derived signaling molecules are temporally and spatially required to coordinate oligodendrocyte differentiation. In this study, we show that neurons regulate myelin membrane trafficking in oligodendrocytes. In the absence of neurons, the major myelin membrane protein, ...

The distribution of newly synthesized proteolipid protein (PLP, 23 kdaltons) and myelin basic proteins (MBPs, 14-21.5 kdaltons) was determined in microsomal and myelin fractions prepared from the brainstems oi 10-30 d-old rats sacrificed at different times after an intracranial injection of 3~S-methionine. Labeled MBPs were found in the myelin fraction 2 min after the injection, whereas PLP app...

Pelizaeus-Merzbacher disease (PMD) can now be defined as an X-linked recessive leukodystrophy that is caused by a mutation in the proteolipid protein (PLP) gene on chromosome Xq22. The most common mutation is gene duplication followed in frequency by missense mutations, insertions, and deletions. The clinical spectrum ranges from severe neonatal cases to relatively benign adult forms and X-link...

Myelin membranes are sheet-like extensions of oligodendrocytes that can be considered membrane domains distinct from the cell's plasma membrane. Consistent with the polarized nature of oligodendrocytes, we demonstrate that transcytotic transport of the major myelin-resident protein proteolipid protein (PLP) is a key element in the mechanism of myelin assembly. Upon biosynthesis, PLP traffics to...