The SMA Modifier Plastin 3 Targets Cell Membrane-Associated Proteins in Motoneurons.

Autor: Jablonka S; Institute of Clinical Neurobiology, University Hospital Würzburg, Würzburg, Germany., Schäfer N; Institute of Clinical Neurobiology, University Hospital Würzburg, Würzburg, Germany.
Jazyk: angličtina
Zdroj: Neuroscience insights [Neurosci Insights] 2024 Jan 19; Vol. 19, pp. 26331055241226623. Date of Electronic Publication: 2024 Jan 19 (Print Publication: 2024).
DOI: 10.1177/26331055241226623
Abstrakt: Loss of the Survival Motor Neuron (SMN) gene inevitably leads to spinal muscular atrophy (SMA), one of the most common fatal neuromuscular diseases in children with FDA and EMA approved therapies. However, the cellular mechanisms leading to neuromuscular junction (NMJ) dysfunction due to impaired Ca 2+ homeostasis in the presynaptic compartment remain largely unexplained. In the last decade, the so-called SMA modifiers have gained attention. The F-actin bundler Plastin 3 (PLS3) is one of them and counteracts neurotransmission defects, including altered vesicle endocytosis, in Smn-deficient NMJs. Properly bundled F-actin is the basis for the translocation and arrangement of transmembrane proteins at the cell surface. Our recently published data by Hennlein et al., J Cell Biol. (2023) clearly showed that Smn deficiency impairs the F-actin dependent translocation of the high-affinity BDNF receptor TrkB to the cell surface resulting in reduced BDNF-mediated TrkB activation in motor axon terminals. Strikingly, the overexpression of PLS3 restores TrkB availability, and significantly improves the clustering of the active zone-associated voltage-gated calcium channel Ca v 2.2 in growth cones of Smn-deficient motoneurons. These observations raise the question of how PLS3 mediates the proper cell surface localization and cluster-like formation of Ca v 2.2 in motor axon terminals.
Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
(© The Author(s) 2024.)
Databáze: MEDLINE
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