JOURNAL CLUB TIBS 25 – AUGUST 2000

organelle – the sensing and transduction

of pro-apoptotic signals. The Golgi
Tooth eruption capable of differentiating in the presence
of locally produced PTHrP. Inhibition of
complex, which lies at the heart of the this endogeneous PTHrP activity with a
secretory pathway, is in the ideal position Tooth eruption represents a unique rabbit anti-human PTHrP(1–34) antiserum
to sense changes in the cell that might example of two correlated, yet completely decreased the spontaneous formation of
indicate perturbations of cellular uncoupled, processes: the formation and osteoclasts to ,30% of the amount found
function. For example, many viruses resorption of bone. By the time a first in control experiments. Expression of
exploit the secretory pathway to their molar starts to be propelled into the oral PTH/PTHrP type I receptor in DF cells
own ends, and it might be that the cavity, the tooth is fully encased within makes them the likely target cells for the
localization of apoptotic signalling dense bone that gradually must be action of PTHrP. Using the fetal rat long-
pathways and effectors to the Golgi removed. Induction of osteoclastic bone bone resorption assay, Nakchbandi and
complex is a partial response. resorption on the coronal tooth co-workers demonstrated that the
Interestingly, many viruses encode surface is an early step in the tooth cultured DF cells could induce bone
inhibitors of apoptosis, which could be eruption pathway. However, the resorption in response to PTHrP by
necessary to evade the surveillance of the process of the onset and regulation secreting a soluble unidentified mediator.
Golgi complex. As the authors of this of tooth eruption on a molecular level They could also show that induced DF
work point out, there is other is far from understood. cells were capable of upregulating the
circumstantial evidence that the Golgi Previous in vivo experiments have expression of osteoclast differentiation
complex might be an important player in provided convincing evidence that tooth factor (ODF) and downregulated its
apoptotic cell death. Golgi membranes eruption fails in the absence of inhibitory counterpart (OCIF). Because
are known to participate in some form of parathyroid hormone-related protein the ODF/OCIF system is known to be
ceramide signalling, and to contain a (PTHrP) action in the microenvironment critical to osteoblast-mediated
number of signalling proteins that are of the tooth. Which cells are responsible stimulation of osteoclasts, DF cells might
known to trigger apoptosis, such as the for the initiation of tooth eruption, and replace osteoblasts in the
tumour necrosis factor receptor. how do they achieve this challenging task microenviroment of the tooth, thus
Whatever the general consequences of its with the help of PTHrP? These questions providing a shortcut to osteoclast
localization, caspase-2 clearly plays a key were addressed by Nakchbandi and co- differentiation.
role in the destruction of the Golgi workers, who observed the spontaneous The work of Nakchbandi et al. connects
complex during apoptosis. formation of fully functional osteoclasts previous published data with newer
The golgins are a family of proteins in the absence of added PTHrP when findings and helps to develop a clear
identified as antigens in a variety of coculturing specialized epithelial and picture of the interplay of various cell
autoimmune conditions, the normal mesenchymal cells surrounding the types and the cascade of mediators
cellular function of which is thought to teeth1. Their work provides new insights allowing tooth eruption. However, certain
be in membrane traffic and maintaining into the process of tooth eruption and questions still remain. Is the DF-cell-
the structure of the Golgi complex. One into the regulatory network of interacting secreted soluble mediator related to ODF?
of these proteins emerges as a specific cells and mediators accompanying this What is the signal that induces SR cells to
target for caspase-2 early in apoptosis, event. increase the PTHrP expression level?
and in cells expressing a form of In a first step, Nakchbandi et al. Determination of the chemical nature of
golgin-160 where the cleavage site confirmed findings that epithelial stellum the soluble mediator might shed light on
has been abolished, the apoptotic reticulum (SR) cells start to produce this putative cellular differentiation factor
destruction of the Golgi complex is abundant amounts of PTHrP mRNA just and is likely to provide clearer insights
retarded. Clearly a case worthy of before tooth eruption, and that into the biochemistry of tooth formation.
further investigation! mesenchymal dental follicle (DF) cells
express mRNA of the PTH/PTHrP type I 1 Nakchbandi, I.A. et al. (2000) Parathyroid hormone-
1 Mancini, M. et al. (2000) Caspase-2 is localised at the receptor. Coculturing of murine DF and SR related protein induces spontaneous osteoclast
Golgi complex and cleaves Golgin-160 during cells resulted in spontaneous osteoclast formation via a paracrine cascade. Proc. Natl. Acad.
apoptosis. J. Cell Biol. 149, 603–612 formation in the absence of added Sci. U. S. A. 97, 7296–7300
osteoclast precursors and without the
FRANCIS A. BARR addition of exogenous PTHrP or vitamin D. PETER BAYER AND BIRGITTA BEATRIX
These data suggest that the primary
Email: [Link]@[Link] cultures contained osteoclast precursors Email: bayer@[Link]

Using genetic screens Mourrain et al.1

Making silence the appearance of short, 21–25-nt, RNAs
derived from the dsRNA itself, as well as and Dalmay et al.2 have now
degradation of any homologous cellular independently reported the discovery of
When challenged with certain nucleic acids mRNA. Intriguingly, following local a gene required for PTGS in Arabidopsis,
such as antisense RNA or transgenes, a initiation of silencing, the effect spreads which shares homology with
variety of organisms respond by silencing throughout the organism and can even be Caenorhabditis elegans and Neurospora
any genes that share homology with the maintained through subsequent crassa proteins previously shown to
foreign nucleic acid. This general generations. Researchers are using control RNAi and quelling, respectively.
phenomenon, originally discovered in genetics to identify the genes responsible These authors have therefore finally
plants where it was called co-suppression for the silencing mechanism and established a firm molecular link between
or post-transcriptional gene silencing biochemical assays to dissect their mode the silencing process in the three classes
(PTGS), also occurs in animal cells where it of action. Phenomenological evidence has of organism. It emerges that the three
is termed RNA interference (RNAi), as well been mounting that the event in animals, related genes resemble a plant protein
as in fungi where it is known as quelling. plants and fungi shares a very similar that has an RNA-directed RNA polymerase
The nucleic acid species that triggers pathway, although, until recently, no activity. It is therefore thought that the
silencing is double-stranded (ds) RNA, silencing genes common to all three role of these proteins is to amplify the
which, when introduced to a cell, leads to organisms had been discovered. RNA inducer of silencing. The

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