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Review
, 2 (9), a000703

Orphan Nuclear Bodies

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Review

Orphan Nuclear Bodies

Maria Carmo-Fonseca et al. Cold Spring Harb Perspect Biol.

Abstract

Orphan nuclear bodies are defined as nonchromatin nuclear compartments that have been less well studied compared with other well-characterized structures in the nucleus. Nuclear bodies have traditionally been thought of as uniform distinct entities depending on the protein "markers" they contain. However, it is becoming increasingly apparent that nuclear bodies enriched in different sets of transcriptional regulators share a link to the ubiquitin-proteasome and SUMO-conjugation pathways. An emerging concept is that some orphan nuclear bodies might act as sites of protein modification by SUMO and/or proteasomal degradation of ubiquitin-tagged proteins. By defining a specialized environment for protein modification and degradation, orphan nuclear bodies may increase the capacity of cells to survive under varying environmental conditions.

Figures

Figure 1.
Figure 1.
The 26S proteasome is composed of one core particle (20S) and one or two regulatory particles (19S). Proteins destined for degradation are initially attached to ubiquitin polymers. After this covalent modification, the substrate protein is able to bind (either directly or via adaptor proteins) to the 19S regulatory complex. Then, the protein is unfolded by ATPases that encircle the entrance of the 20S catalytic core, and the polyubiquitin chain is removed by proteasome-associated deubiquitylating enzymes. Finally, the unfolded protein is translocated into the central proteolytic chamber, where it is cleaved into short peptides.
Figure 2.
Figure 2.
The clastosome is a nuclear body enriched in proteasomes. (A,B) Colocalization of ubiquitin-conjugates (A, red staining) and 19S proteasomal complexes (A and B, green staining) in a human neuron mechanically isolated from dorsal root ganglia obtained from an autopsy of a patient without any diagnosed neurological disorder. Bar, 5 µm. (C, D) Several clastosomes are observed in the nucleus of a neurosecretory neuron isolated from rat hypothalamus after osmotic stress; double-immunofluorescence with antibodies specific to 20S proteasomal complexes (C and D, red staining) and a nucleoporin (C, green staining). (E) Immunogold labeling with antibodies directed against the 20S proteasome reveals a doughnut- or ring-shaped nuclear body. Bar, 300 nm.
Figure 3.
Figure 3.
Clastosomes concentrate protein substrates for proteasomal degradation. (A, B) The panels depict a human neuron mechanically isolated from dorsal root ganglia obtained from an autopsy of a patient without any diagnosed neurological disorder, double-labeled with anti-PML (B, green staining) and anti-20S proteasomal complexes (A and B, red staining). Note that only one of the multiple PML bodies concentrates proteasomes (arrowhead) and that one body enriched in proteasomes does not contain PML (arrow). (C, D) Colocalization of 19S proteasomal complexes (C and D, red staining) and c-Fos (D, green staining) in the nucleus of a neurosecretory neuron isolated from rat hypothalamus after osmotic stress. Bar, 5 µm. (E) Hypothetical model for PML protein traffic through PML bodies and clastosomes. PML (blue spheres) distributes diffusely in the nucleoplasm and associates transiently with primary PML bodies. Upon modification by SUMO and ubiquitin, the modified PML proteins (red spheres) are recruited to clastosomes for degradation.
Figure 4.
Figure 4.
SUMO-1 localizes to nuclear bodies in neuron-like UR61 cells. (A) Electron microscopy reveals the presence of a round body (arrow) in the nucleus (nu, nucleolus). Bar, 1 µm. (B) Immunogold labeling of a nuclear body using antibodies specific for SUMO-1 (an arrow points to an adjacent doughnut-shaped structure that is most probably a clastosome). Bar, 300 nm. (C) The distribution of SUMO-1 is detected in green by immunofluorescence; the nucleolus is blue (immunofluorescence with antifibrillarin antibody) and the cell periphery is red (Rhodamine-Phalloidin Staining). (D) Colocalization of GFP-SUMO-1 (green) and SUMO E2 conjugating enzyme DsRed-Ubc9 (red) in nuclear bodies; the cytoplasm is stained blue (immunofluorescence with anti-SMN antibody). Bar, 5 µm.
Figure 5.
Figure 5.
The RNA-binding protein Sam68 localizes to nuclear bodies in both Hela cells (A) and rat neurons (B, C). Sam 68 is detected in green by immunofluorescence labeling. Nucleoli and cytoplasm are detected in red (propidium iodide staining). RNA splicing speckles are detected in blue (immunofluorescence with an antibody directed against the 2, 2, 7-trimethylguanosine cap structure of snRNAs). Bar, 10 µm.

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