The polarity protein Par-3 directly interacts with p75NTR to regulate myelination.
Cell polarity is critical in various cellular processes ranging from cell migration to asymmetric cell division and axon and dendrite specification. Similarly, myelination by Schwann cells is polarized, but the mechanisms involved remain unclear. Here, we show that the polarity protein Par-3 localizes asymmetrically in Schwann cells at the axon-glial junction and that disruption of Par-3 localization, by overexpression and knockdown, inhibits myelination. Additionally, we show that Par-3 directly associates and recruits the p75 neurotrophin receptor to the axon-glial junction, forming a complex necessary for myelination. Together, these results point to a critical role in the establishment of cell polarity for myelination.
Chan
Jonah R
JR
Department of Cell and Neurobiology, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles 90089, USA. jonah.chan@usc.edu
Jolicoeur
Christine
C
Yamauchi
Junji
J
Elliott
Jimmy
J
Fawcett
James P
JP
Ng
Benjamin K
BK
Cayouette
Michel
M
D020816:Amino Acid Motifs; D000818:Animals; D001369:Axons / Q000737:chemistry / Q000648:ultrastructure; D019208:Brain-Derived Neurotrophic Factor / Q000502:physiology; D002352:Carrier Proteins / Q000032:analysis / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016764:Cell Polarity; D002478:Cells, Cultured; D018920:Coculture Techniques; D005727:Ganglia, Spinal / Q000648:ultrastructure; D007365:Intercellular Junctions / Q000737:chemistry; D051379:Mice; D009186:Myelin Sheath / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D051381:Rats; D017978:Receptors, Growth Factor / Q000737:chemistry / Q000378:metabolism*; D012583:Schwann Cells / Q000166:cytology / Q000502:physiology* / Q000648:ultrastructure
D019208:Brain-Derived Neurotrophic Factor; D002352:Carrier Proteins; D009419:Nerve Tissue Proteins; C472451:Pard3 protein, rat; D017978:Receptors, Growth Factor; C068313:Ngfr protein, rat