The spinal muscular atrophy gene product regulates actin dynamics.
Survival of Motoneuron (SMN) protein
actin
actin dynamics
profilin2a
spinal muscular atrophy (SMA)
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN: 1530-6860
Titre abrégé: FASEB J
Pays: United States
ID NLM: 8804484
Informations de publication
Date de publication:
30 Sep 2024
30 Sep 2024
Historique:
revised:
31
07
2024
received:
01
02
2023
accepted:
04
09
2024
medline:
21
9
2024
pubmed:
21
9
2024
entrez:
21
9
2024
Statut:
ppublish
Résumé
Spinal Muscular Atrophy (SMA) is a neuromuscular disease caused by low levels of the Survival of Motoneuron (SMN) protein. SMN interacts with and regulates the actin-binding protein profilin2a, thereby influencing actin dynamics. Dysfunctional actin dynamics caused by SMN loss disrupts neurite outgrowth, axonal pathfinding, and formation of functional synapses in neurons. Whether the SMN protein directly interacts with and regulates filamentous (F-) and monomeric globular (G-) actin is still elusive. In a quantitative single cell approach, we show that SMN loss leads to dysregulated F-/G-actin fractions. Furthermore, quantitative assessment of cell morphology suggests an F-actin organizational defect. Interestingly, this is mediated by an interaction of SMN with G- and F-actin. In co-immunoprecipitation, in-vitro pulldown and co-localization assays, we elucidated that this interaction is independent of the SMN-profilin2a interaction. Therefore, we suggest two populations being relevant for functional actin dynamics in healthy neurons: SMN-profilin2a-actin and SMN-actin. Additionally, those two populations may influence each other and therefore regulate binding of SMN to actin. In SMA, we showed a dysregulated co-localization pattern of SMN-actin which could only partially rescued by SMN restoration. However, dysregulation of F-/G-actin fractions was reduced by SMN restoration. Taken together, our results suggest a novel molecular function of SMN in binding to actin independent from SMN-profilin2a interaction.
Identifiants
pubmed: 39305126
doi: 10.1096/fj.202300183R
doi:
Substances chimiques
Actins
0
Profilins
0
Survival of Motor Neuron 1 Protein
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e70055Subventions
Organisme : Deutsche Forschungsgemeinschaft (DFG)
ID : PO732
Organisme : Deutsche Forschungsgemeinschaft (DFG)
ID : ZE994
Organisme : European Research Council (ERC)
ID : 956185
Organisme : Konrad-Adenauer-Stiftung (KAS)
Informations de copyright
© 2024 Federation of American Societies for Experimental Biology.
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