PUBLICATION
The perinuclear region concentrates disordered proteins with predicted phase separation distributed in a 3D network of cytoskeletal filaments and organelles
- Authors
- do Amaral, M.J., de Andrade Rosa, I., Andrade, S.A., Fang, X., Andrade, L.R., Costa, M.L., Mermelstein, C.
- ID
- ZDB-PUB-211231-1
- Date
- 2022
- Source
- Biochimica et biophysica acta. Molecular cell research 1869: 119161 (Journal)
- Registered Authors
- Costa, Manoel Luis, Mermelstein, Claudia
- Keywords
- Biomolecular condensates, Intrinsically disordered protein/region, Liquid-liquid phase separation, Membraneless organelles, Nuclear cloud, Perinuclear
- MeSH Terms
-
- Actin Cytoskeleton/genetics
- Actin Cytoskeleton/metabolism*
- Actin Cytoskeleton/ultrastructure
- Animals
- Cells, Cultured
- Chick Embryo
- Intrinsically Disordered Proteins/metabolism
- Lysosomes/metabolism
- Lysosomes/ultrastructure
- Microscopy, Electron, Transmission/methods
- Mitochondria/metabolism
- Mitochondria/ultrastructure
- Nuclear Envelope/metabolism*
- Nuclear Envelope/ultrastructure
- Proteome/genetics
- Proteome/metabolism
- Zebrafish
- PubMed
- 34655689 Full text @ BBA Molecular Cell Research
Citation
do Amaral, M.J., de Andrade Rosa, I., Andrade, S.A., Fang, X., Andrade, L.R., Costa, M.L., Mermelstein, C. (2022) The perinuclear region concentrates disordered proteins with predicted phase separation distributed in a 3D network of cytoskeletal filaments and organelles. Biochimica et biophysica acta. Molecular cell research. 1869:119161.
Abstract
Membraneless organelles have emerged during the evolution of eukaryotic cells as intracellular domains in which multiple proteins organize into complex structures to perform specialized functions without the need of a lipid bilayer compartment. Here we describe the perinuclear space of eukaryotic cells as a highly organized network of cytoskeletal filaments that facilitates assembly of biomolecular condensates. Using bioinformatic analyses, we show that the perinuclear proteome is enriched in intrinsic disorder with several proteins predicted to undergo liquid-liquid phase separation. We also analyze immunofluorescence and transmission electron microscopy images showing the association between the nucleus and other organelles, such as mitochondria and lysosomes, or the labeling of specific proteins within the perinuclear region of cells. Altogether our data support the existence of a perinuclear dense sub-micron region formed by a well-organized three-dimensional network of structural and signaling proteins, including several proteins containing intrinsically disordered regions with phase behavior. This network of filamentous cytoskeletal proteins extends a few micrometers from the nucleus, contributes to local crowding, and organizes the movement of molecular complexes within the perinuclear space. Our findings take a key step towards understanding how membraneless regions within eukaryotic cells can serve as hubs for biomolecular condensates assembly, in particular the perinuclear space. Finally, evaluation of the disease context of the perinuclear proteins revealed that alterations in their expression can lead to several pathological conditions, and neurological disorders and cancer are among the most frequent.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping