Low-density lipoprotein receptor-related protein 1 is an essential receptor for myelin phagocytosis

J Cell Sci. 2009 Apr 15;122(Pt 8):1155-62. doi: 10.1242/jcs.040717. Epub 2009 Mar 19.


Multiple sclerosis (MS) is an autoimmune disease in which myelin is progressively degraded. Because degraded myelin may both initiate and accelerate disease progression, clearing degraded myelin from extracellular spaces may be critical. In this study, we prepared myelin vesicles (MV) from rat brains as a model of degraded myelin. Murine embryonic fibroblasts (MEFs) rapidly internalized MVs, which accumulated in lysosomes only when these cells expressed low-density lipoprotein receptor-related protein (LRP1). Receptor-associated protein (RAP), which binds LRP1 and inhibits interaction with other ligands, blocked MV uptake by LRP1-expressing MEFs. As a complementary approach, we prepared primary cultures of rat astrocytes, microglia and oligodendrocytes. All three cell types expressed LRP1 and mediated MV uptake, which was inhibited by RAP. LRP1 gene-silencing in oligodendrocytes also blocked MV uptake. Myelin basic protein (MBP), which was expressed as a recombinant protein, bound directly to LRP1. MBP-specific antibody inhibited MV uptake by oligodendrocytes. In experimental autoimmune encephalomyelitis in mice, LRP1 protein expression was substantially increased in the cerebellum and spinal cord. LRP1 colocalized with multiple CNS cell types. These studies establish LRP1 as a major receptor for phagocytosis of degraded myelin, which may function alone or in concert with co-receptors previously implicated in myelin phagocytosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Cells, Cultured
  • Central Nervous System / metabolism*
  • Cerebellum / metabolism
  • Encephalomyelitis, Autoimmune, Experimental / metabolism*
  • Humans
  • Ligands
  • Low Density Lipoprotein Receptor-Related Protein-1 / genetics
  • Low Density Lipoprotein Receptor-Related Protein-1 / metabolism*
  • Lysosomes / metabolism
  • Mice
  • Myelin Basic Protein / metabolism
  • Myelin Sheath / metabolism*
  • Neuroglia / metabolism
  • Phagocytosis*
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, LDL / metabolism
  • Spinal Cord / metabolism
  • Transfection
  • Tumor Suppressor Proteins / metabolism
  • rap GTP-Binding Proteins / metabolism


  • Ligands
  • Low Density Lipoprotein Receptor-Related Protein-1
  • Lrp1 protein, mouse
  • Myelin Basic Protein
  • RNA, Small Interfering
  • Receptors, LDL
  • Tumor Suppressor Proteins
  • rap GTP-Binding Proteins