Endoplasmic reticulum network heterogeneity guides diffusive transport and kinetics.
Journal
Biophysical journal
ISSN: 1542-0086
Titre abrégé: Biophys J
Pays: United States
ID NLM: 0370626
Informations de publication
Date de publication:
08 08 2023
08 08 2023
Historique:
received:
09
02
2023
revised:
17
05
2023
accepted:
28
06
2023
pmc-release:
08
08
2024
medline:
11
8
2023
pubmed:
4
7
2023
entrez:
4
7
2023
Statut:
ppublish
Résumé
The endoplasmic reticulum (ER) is a dynamic network of interconnected sheets and tubules that orchestrates the distribution of lipids, ions, and proteins throughout the cell. The impact of its complex, dynamic morphology on its function as an intracellular transport hub remains poorly understood. To elucidate the functional consequences of ER network structure and dynamics, we quantify how the heterogeneity of the peripheral ER in COS7 cells affects diffusive protein transport. In vivo imaging of photoactivated ER membrane proteins demonstrates their nonuniform spreading to adjacent regions, in a manner consistent with simulations of diffusing particles on extracted network structures. Using a minimal network model to represent tubule rearrangements, we demonstrate that ER network dynamics are sufficiently slow to have little effect on diffusive protein transport. Furthermore, stochastic simulations reveal a novel consequence of ER network heterogeneity: the existence of "hot spots" where sparse diffusive reactants are more likely to find one another. ER exit sites, specialized domains regulating cargo export from the ER, are shown to be disproportionately located in highly accessible regions, further from the outer boundary of the cell. Combining in vivo experiments with analytic calculations, quantitative image analysis, and computational modeling, we demonstrate how structure guides diffusive protein transport and reactions in the ER.
Identifiants
pubmed: 37401053
pii: S0006-3495(23)00410-1
doi: 10.1016/j.bpj.2023.06.022
pmc: PMC10432226
pii:
doi:
Substances chimiques
Proteins
0
Types de publication
Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3191-3205Informations de copyright
Copyright © 2023 Biophysical Society. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
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