Structural and functional compartmentalization of the cell nucleus in supraoptic neurons

Abstract

It is well-established that the neuronal cell nucleus is organized in discrete compartments involved in transcription and RNA processing. The main nuclear compartments in neurons include the chromosome territories, the nucleolus, nuclear speckles of splicing factors, Cajal bodies, and nuclear rodlets. The supraoptic nucleus (SON) neurons provide a powerful model in vivo to study the organization of these nuclear compartments in response to variations of cellular activity. The upregulation of transcription in SON neurons under chronic hyperosmolar conditions is associated with 1) nuclear and nucleolar enlargement, 2) dispersion of chromatin, 3) reduction in the size of nuclear speckles, 4) increase in the number of Cajal bodies implicated in the maturation of splicing small nuclear ribonucleoproteins, and 5) proliferation of the fibrillar centers of the nucleolus, the sites of nucleolar transcription of ribosomal genes. These changes revert after the cessation of the activation by rehydration of animals. Under conditions of neuronal stress induced by hypertonic saline injection, SON neurons exhibit an early response of downregulation of transcription. This is accompanied by chromatin condensation, redistribution of splicing factors, reduction in the number of Cajal bodies, and microsegregation of the fibrillar and granular components of the nucleolus and disruption of its fibrillar centers, all of which are associated with a transitory expression of c-Fos. These changes progressively revert and at 24 hours after the stress induction a rebound upregulation of transcription is observed. These findings illustrate the transcription-dependent organization and behavior of nuclear compartments in the neuronal model of magnocellular neurosecretory cells of the hypothalamus.

Trafficking of tachykinin neurokinin 3 receptor to nuclei of neurons in the paraventricular nucleus of the hypothalamus following osmotic challenge

“…This adds to the idea of a possible interaction of NK3R with paraspeckle proteins because the NK3R was also detected within the nucleolus of these neurons. Interestingly, several studies show that osmotic challenge dramatically affects the morphology of the nucleolus (Armstrong et al, 1977) and that this change is related to ribosome biogenesis to support the synthesis of new hormone peptides (Berciano et al, 2002). The association of the NK3R with these nuclear organelles strengthens the hypothesis that the receptor is playing an active role in gene expression within the nucleus of neurons after it has been activated and internalized.…”

Rearrangement of nuclear ribonucleoprotein (RNP)‐containing structures during apoptosis and transcriptional arrest

“…In a series of accurate and elegant papers, Lafarga and coworkers (Pena et al, 2001;Berciano et al, 2002) followed the modification of the transcription and splicing machinery 610 M. Biggiogera et al / Biology of the Cell 96 (2004) 603-615 in neurons: following hyperosmotic stress in supraoptic neurons, they observed (along with other changes) a redistribution of splicing factors and a reduction in the number of Cajal (coiled) bodies, and suggested that a "transcriptiondependent organization and behavior of nuclear compartments" should exist (Berciano et al, 2002). The rearrangement of nuclear and nucleolar RNPs has also been related to terminal differentiation and death of normal hemopoietic and leukemic cells (Smetana, 2002;Smetana and Hrkal, 2003;Smetana et al, 2001Smetana et al, , 2002.…”

Reorganization of nuclear compartments of type A neurons of trigeminal ganglia in response to inflammatory injury of peripheral nerve endings

“…Transient chromatin condensation has also been reported in response to transcriptional inhibition induced by osmotic stress in supraoptic neurons (Lafarga et al, 1998;Berciano et al, 2002). The existence of gene silencing in type A neurons within 3 days-pi is also supported by the notable reduction in the expression level of histone H4 acetylated, which is involved in nucleosome remodelling of active chromatin domains (Gregory et al, 2001;Roth et al, 2001;Jaskelioff & Craig, 2003).…”

“…Given that increased c-Jun expression was associated with a reduction in nuclear activity in other experimental models of neuronal injury (Pena et al, 2000;Berciano et al, 2002), we next investigated whether the inflammatory injury of nerve endings produced a reorganization of active and inactive chromatin in type A trigeminal neurons. We used double labelling experiments to detect pan-histone, as a marker of whole chromatin, and acetylated H4 histone, which was found to be associated with transcriptionally active chromatin (Gregory et al, 2001).…”