| Title: |
Spectrin condensates provide a nidus for assembling the axonal membrane-associated periodic skeleton |
| Authors: |
Boyer, Nicholas, P; Sharma, Rohan; Wiesner, Theresa; Parperis, Christopher; Delamare, Antoine; Pelletier, Florence; Jullien, Nicolas; Bhatt, Anshul, M; Parra-Rivas, Leonardo, A; Kearney, Patrick, J; Shavarebi, Farbod; Leterrier, Christophe; Roy, Subhojit |
| Contributors: |
Department of Pathology Univ California San Diego (UC San Diego); School of Medicine Univ California San Diego (UC San Diego); University of California San Diego (UC San Diego); University of California (UC)-University of California (UC)-University of California San Diego (UC San Diego); University of California (UC)-University of California (UC); Institut de neurophysiopathologie (INP); Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS); Department of Neurosciences Univ California San Diego (Neuro - UC San Diego); Fondation pour la Recherche sur le Cerveau FRC AOE 16 “Espoir en tête” 2021; Fondation pour la recherche médicale FRM EQ20210301296; NeuroMarseille AMIDEX AMX-19-IET-004; Marseille Imaging A*MIDEX AMX-19-IET-002; CPER-FEDER Plateforme NeuroTimone PA0014842; ANR-20-CE13-0024,ASHA,L'échafaudage d'actine/spectrine façonne la physiologie de l'axone(2020); ANR-20-CE16-0021,SPEED-Y,Comprendre le rôle du cycle de détyrosination/re-tyrosination de la tubuline dans la plasticité synaptique(2020); ANR-21-CE42-0015,5D-SURE,Microscopie de fluorescence super-résolue 5D pour la biologie(2021); ANR-11-IDEX-0001,Amidex,INITIATIVE D'EXCELLENCE AIX MARSEILLE UNIVERSITE(2011) |
| Source: |
EISSN: 2589-0042 ; iScience ; https://amu.hal.science/hal-05489614 ; iScience, 2026, 29, ⟨10.1016/j.isci.2025.114454⟩ |
| Publisher Information: |
CCSD; Elsevier |
| Publication Year: |
2026 |
| Collection: |
Aix-Marseille Université: HAL |
| Subject Terms: |
[SDV]Life Sciences [q-bio] |
| Description: |
International audience ; In axons, α/β-spectrins, adducin, and actin filaments assemble into a lattice underneath the plasma membrane, but the mechanistic events leading to this membrane-associated periodic skeleton (MPS) are unclear. Visualizing MPS-components in developing axons, we found distal focal patches containing spectrins and adducin (but sparse actin filaments) with biophysical properties reminiscent of biomolecular condensation. Overexpressing spectrin repeats – constituents of α/β-spectrins – in heterologous cells triggered condensate formation, and preventing the association of βII-spectrin with actin filaments or membranes also facilitated condensation. Introducing a stretch of spectrin-repeats in neurons before MPS establishment triggered ectopic condensate-like structures in the soma and disrupted the axonal lattice, advocating a functional role for bio- molecular condensation. We propose a condensation-assembly model where spectrin-repeats trigger focal phase separated condensates, providing a nidus for MPS assembly that recruits actin filaments to ultimately generate the stable lattice. Our overall model is supported by recent studies showing phase-separation via coiled-coil domains and recruitment/polymerization of actin by other condensate-forming proteins. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1016/j.isci.2025.114454 |
| Availability: |
https://amu.hal.science/hal-05489614; https://amu.hal.science/hal-05489614v1/document; https://amu.hal.science/hal-05489614v1/file/PIIS2589004225027154%20%281%29.pdf; https://doi.org/10.1016/j.isci.2025.114454 |
| Rights: |
https://creativecommons.org/licenses/by-nc-nd/4.0/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.AC66133E |
| Database: |
BASE |