Nucleolin regulates 14-3-3ζ mRNA and promotes cofilin phosphorylation to induce tunneling nanotube formation.
14-3-3 Proteins
/ genetics
3' Untranslated Regions
Actin Depolymerizing Factors
/ genetics
Animals
Caenorhabditis elegans
/ genetics
Caenorhabditis elegans Proteins
/ genetics
Cell Communication
Cell Line, Tumor
Humans
Nanotubes
Phosphoproteins
/ genetics
Phosphorylation
RNA-Binding Proteins
/ genetics
Nucleolin
MSec
RNA-binding domains
cofilin
intercellular communication
mRNA regulation
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:
01 2021
01 2021
Historique:
received:
08
05
2020
revised:
19
10
2020
accepted:
02
11
2020
pubmed:
23
11
2020
medline:
16
6
2021
entrez:
22
11
2020
Statut:
ppublish
Résumé
Tunneling nanotubes (TNTs) mediate intercellular communication between animal cells in health and disease, but the mechanisms of their biogenesis and function are poorly understood. Here we report that the RNA-binding protein (RBP) nucleolin, which interacts with the known TNT-inducing protein MSec, is essential for TNT formation in mammalian cells. Nucleolin, through its RNA-binding domains (RBDs), binds to and maintains the cytosolic levels of 14-3-3ζ mRNA, and is, therefore, required for TNT formation. A specific region of the 3'-untranslated region (UTR) of the 14-3-3ζ mRNA is likely to be involved in its regulation by nucleolin. Functional complementation experiments suggest that nucleolin and 14-3-3ζ form a linear signaling axis that promotes the phosphorylation and inactivation of the F-actin depolymerization factor cofilin to induce TNT formation. MSec also similarly inactivates cofilin, but potentiates TNT formation independent of the nucleolin-14-3-3ζ axis, despite biochemically interacting with both proteins. We show that 14-3-3ζ and nucleolin are required for the formation of TNTs between primary mouse neurons and astrocytes and in multiple other mammalian cell types. We also report that the Caenorhabditis elegans orthologs of 14-3-3ζ and MSec regulate the size and architecture of the TNT-like cellular protrusions of the distal tip cell (DTC), the germline stem cell niche in the gonad. Our study demonstrates a novel and potentially conserved mRNA-guided mechanism of TNT formation through the maintenance of cellular 14-3-3ζ mRNA levels by the RBP nucleolin.
Identifiants
pubmed: 33222276
doi: 10.1096/fj.202001152R
doi:
Substances chimiques
14-3-3 Proteins
0
3' Untranslated Regions
0
Actin Depolymerizing Factors
0
Caenorhabditis elegans Proteins
0
Phosphoproteins
0
RNA-Binding Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e21199Subventions
Organisme : Foundation for the National Institutes of Health (FNIH)
ID : NCI [CA175794]
Informations de copyright
© 2020 Federation of American Societies for Experimental Biology.
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