| First Author | Hennlein L | Year | 2023 |
| Journal | J Cell Biol | Volume | 222 |
| Issue | 3 | PubMed ID | 36607273 |
| Mgi Jnum | J:347483 | Mgi Id | MGI:7509008 |
| Doi | 10.1083/jcb.202204113 | Citation | Hennlein L, et al. (2023) Plastin 3 rescues cell surface translocation and activation of TrkB in spinal muscular atrophy. J Cell Biol 222(3) |
| abstractText | Plastin 3 (PLS3) is an F-actin-bundling protein that has gained attention as a modifier of spinal muscular atrophy (SMA) pathology. SMA is a lethal pediatric neuromuscular disease caused by loss of or mutations in the Survival Motor Neuron 1 (SMN1) gene. Pathophysiological hallmarks are cellular maturation defects of motoneurons prior to degeneration. Despite the observed beneficial modifying effect of PLS3, the mechanism of how it supports F-actin-mediated cellular processes in motoneurons is not yet well understood. Our data reveal disturbed F-actin-dependent translocation of the Tropomyosin receptor kinase B (TrkB) to the cell surface of Smn-deficient motor axon terminals, resulting in reduced TrkB activation by its ligand brain-derived neurotrophic factor (BDNF). Improved actin dynamics by overexpression of hPLS3 restores membrane recruitment and activation of TrkB and enhances spontaneous calcium transients by increasing Cav2.1/2 "cluster-like" formations in SMA axon terminals. Thus, our study provides a novel role for PLS3 in supporting correct alignment of transmembrane proteins, a key mechanism for (moto)-neuronal development. |
