LNX1 is a perisynaptic Schwann cell specific E3 ubiquitin ligase that interacts with ErbB2.
Non-myelinating perisynaptic Schwann cells wrap motor axon terminals and are required for both functional and structural integrity of the neuromuscular junction. Several lines of evidence indicate that fine-tuning of neuregulin-1/ErbB signaling is critical for maintaining perisynaptic Schwann cells at synapses and that this control may be achieved by the developmental downregulation of the ErbB2 receptor. Here, we identify a direct interaction between ErbB2 and LNX1, an E3 ubiquitin ligase that can target interacting proteins for degradation through ubiquitination. Immunostaining shows that LNX1 is specifically localized in perisynaptic Schwann cells but not in Schwann cells along the motor axon. Developmentally, levels of LNX1 protein are inversely correlated with the responsiveness of perisynaptic Schwann cells to neuregulin-1. Furthermore, the LNX1 staining disappears upon denervation, whereas ErbB2 reappears in Schwann cells after denervation. Taken together, these data suggest that LNX1 may play a role in regulating neuregulin-1/ErbB signaling in perisynaptic Schwann cells.
Young
Paul
P
Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA.
Nie
Jing
J
Wang
Xueyong
X
McGlade
C Jane
CJ
Rich
Mark M
MM
Feng
Guoping
G
D000818:Animals; D000831:Animals, Newborn; D019556:COS Cells; D002352:Carrier Proteins / Q000502:physiology*; D002522:Chlorocebus aethiops; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D009419:Nerve Tissue Proteins / Q000502:physiology; D020890:Neuregulin-1; D011994:Recombinant Proteins / Q000378:metabolism; D012583:Schwann Cells / Q000187:drug effects / Q000502:physiology*; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D014162:Transfection; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
D002352:Carrier Proteins; C498804:Erbb2ip protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D020890:Neuregulin-1; C490581:Nrg1 protein, mouse; D011994:Recombinant Proteins; D013779:Tetrodotoxin; C111865:Lnx1 protein, mouse; D044767:Ubiquitin-Protein Ligases