Identification and functional characterization of mouse TPO1 as a myelin membrane protein

Brain Res. 2006 Jan 27;1070(1):1-14. doi: 10.1016/j.brainres.2005.11.069. Epub 2006 Jan 6.


TPO1 is a member of the AIGP family, a unique group of proteins that contains 11 putative transmembrane domains. Expression of the rat TPO1 gene is upregulated in cultured oligodendrocytes (OLs) during development from pro-oligodendroblasts to postmitotic OLs. However, the distribution of native TPO1 protein in cultured OLs and in the brain has not been elucidated. We investigated the distribution and cellular function of TPO1 in myelinating cells of the nervous system. In mice, TPO1 gene expression was detected in the central (CNS) and peripheral (PNS) nervous systems and was markedly upregulated at postnatal days 10-20, an early phase of myelination in the mouse brain. To investigate TPO1 localization, we generated affinity-purified antibodies to synthetic peptides derived from mouse TPO1. Immunohistochemical analysis showed that TPO1 was expressed in OLs and Schwann cells but not in neurons and astrocytes. Schwann cells from trembler mice, which lack PNS myelin, had significantly decreased TPO1 expression and an altered localization pattern, suggesting that TPO1 is a functional myelin membrane protein. In OL lineage cell cultures, TPO1 was detected in A2B5+ bipolar early progenitors, A2B5+ multipolar Pro-OLs, GalC+ immature OLs and MBP+ mature OLs. The subcellular localization of TPO1 in OL lineage cells was mapped to the GM130+ Golgi in cell bodies and Fyn+ cell processes and myelin-like sheets. Furthermore, TPO1 selectively colocalized with non-phosphorylated Fyn and promoted Fyn autophosphorylation in COS7 cells, suggesting that TPO1 may play a role in myelin formation via Fyn kinase activation in the PNS and CNS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / metabolism
  • Animals
  • Animals, Newborn
  • Antibodies, Monoclonal / pharmacology
  • Brain / growth & development
  • Brain / metabolism
  • COS Cells
  • Cells, Cultured
  • Chlorocebus aethiops
  • Cross-Linking Reagents / pharmacology
  • Golgi Apparatus / metabolism
  • Membrane Proteins / metabolism
  • Membrane Proteins / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Neurologic Mutants / metabolism
  • Myelin Sheath / physiology*
  • Myelin-Associated Glycoprotein / immunology
  • Nerve Tissue Proteins / metabolism
  • Nerve Tissue Proteins / physiology*
  • Neurons / metabolism
  • Neurons / physiology*
  • Oligodendroglia / metabolism
  • Peripheral Nerves / growth & development
  • Peripheral Nerves / metabolism
  • Phosphorylation
  • Protein Processing, Post-Translational / drug effects
  • Proto-Oncogene Proteins c-fyn / metabolism
  • Rats
  • Schwann Cells / metabolism
  • Tissue Distribution


  • Antibodies, Monoclonal
  • Cross-Linking Reagents
  • Membrane Proteins
  • Myelin-Associated Glycoprotein
  • Nerve Tissue Proteins
  • TPO1 protein, mouse
  • Proto-Oncogene Proteins c-fyn