PirB inhibits axonal outgrowth via the PI3K/Akt/mTOR signaling pathway

Abstract

Accumulating data strongly suggests that leukocyte immunoglobulin like receptor B1 (PirB) inhibits axonal outgrowth. However, the underlying mechanisms remain unclear. In the present study, cortical neurons of newborn mice were cultured with Nogo‑66 (Nogo‑p4; 4 µmol/l; a PirB ligand) together with NEP1‑40 (Nogo inhibitory peptide) and/or anti‑PirB body (50 mg/ml). PirB mRNA and protein was higher in cultured neurons induced by Nogo‑66 compared with untreated cells. Neurite outgrowth assays demonstrated that the inhibitory effects of Nogo‑66 on axonal outgrowth were reversed by anti‑PirB body. Reverse transcription‑quantitative polymerase chain reaction and western blot assays demonstrated that anti‑PirB treatment led to reduced mRNA and protein expression of phosphoinositide 3‑kinase (PI3K), Akt serine/threonine kinase (Akt), mechanistic target of rapamycin kinase (mTOR), myosin IIA and cofilin, which are involved in axonal outgrowth. Furthermore, blockade of the PI3K/Akt/mTOR pathway using a PI3K inhibitor or an mTOR inhibitor diminished the stimulatory effect of anti‑PirB on axonal outgrowth, and the reduced effect of anti‑PirB on factors that were activation by anti‑PirB. In addition, blockade of PI3K/Akt/mTOR enhanced anti‑PirB‑induced gene and protein expression. These results revealed that PirB functions as a potential suppressor in axonal outgrowth via repressing PI3K/Akt/mTOR signaling pathway, and PirB/PI3K/Akt/mTOR may be a novel target for enhancing axonal outgrowth for developing rational therapeutic strategies.

Progesterone attenuates neurological deficits and exerts a protective effect on damaged axons via the PI3K/AKT/mTOR-dependent pathway in a mouse model of intracerebral hemorrhage

“…Another study confirmed that elevated microRNA 29a precursor (miR-29a) could promote axonal outgrowth and neurological recovery after ICH by activating the PI3K/AKT/mTOR pathway [ 50 ]. Additionally, leukocyte immunoglobulin-like receptor B1 (PirB) inhibits axonal outgrowth and is involved in the inhibition of the PI3K/AKT/mTOR pathway [ 51 ]. This evidence suggests that the PI3K/AKT/mTOR pathway plays a crucial role in regulating axonal regeneration in mammals.…”

NCAM regulates the proliferation, apoptosis, autophagy, EMT, and migration of human melanoma cells via the Src/Akt/mTOR/cofilin signaling pathway

“…As NCAM was reported to initiate Src and Akt/mTOR signaling pathways which have regulatory effects on cofilin activation in multiple cells, [25][26][27][28] it is probable that NCAM regulates the activation of cofilin in human F I G U R E 3 NCAM knockdown suppressed the EMT-like phenotype in A375 and M102 cells. (A) The cell morphology transformation of A375 and M102 cells transfected with NCAM downregulation vectors.…”

White-matter repair: Interaction between oligodendrocytes and the neurovascular unit

“…Through alternate downstream pathways, the neuronal receptor paired Ig-like receptor B, which has common ligands with Nogo-66 receptor-1 (NgR1), can prevent the lengthening of axons. [ 17 18 19 ] Axonal growth is also blocked by a combination of the Rho/ROCK pathway and interactions between the sphingosine-1-phosphate receptor 2 in neurons and a specific Nogo-A region. [ 20 ] By helping NgR1 mature and utilizing the Rho/ROCK pathway, the nociception receptor ORL1 also hampers axon extension.…”