The cell is a highly organized factory where each constituent has its place and a role to play. If one piece of this machinery falters, the whole cell is imperiled. The least anomaly may result in an uncontrolled cell likely to engender a variety of diseases, such as cancers.
At the Institut Curie, CNRS researchers, in collaboration with a group at the University of Seville, have just shown that the protein GMAP-210 is the "foreman" essential to maintenance of the integrity and localization of the Golgi apparatus at the heart of the cell. This discovery, published in the August 6 issue of Cell, should enhance our understanding of how the cellular machinery works.
The cell is a miniature factory full of "machines" each with its own precise role to play: the endoplasmic reticulum(1) produces the linchpins of the cell, proteins. The Golgi apparatus (see box opposite) modifies, sorts and assigns them their tasks. Mitochondria supply energy. The cytoskeleton forms the cell’s backbone and ensures the movements of the different cell components. To be "operational", these little machines are constantly "exerting" themselves: they fulfill their function, interact, communicate, keep an eye on each other. In reality, cellular stability masks a hive of activity. This constant cellular activity demands great reliability since if an anomaly arises and persists, the whole cell may be endangered. The least malfunction of the cogwheels of the cellular machinery may give rise to defective cells likely to give rise to various diseases, including cancers.
The Golgi apparatus: eternal renewalThe team of Michel Bornens(2) at the Institut Curie, in collaboration with the group of Rosa Rios at the University of Seville(3), is studying the dynamics of the Golgi apparatus which, like other cellular machinery, works "round the clock". In addition to its task marshalling proteins, the Golgi apparatus renews itself three to four times per cell cycle. These two operations are underpinned by permanent communication between the Golgi apparatus and the endoplasmic reticulum. The latter supplies both the proteins which transit the Golgi apparatus on their way to their destinations and pre-Golgi structures that serve to renew the Golgi apparatus. These pre-Golgi elements are constantly transported from the endoplasmic reticulum via the network of microtubules(1) which leads to the centrosome(1) – the "geographical" center of the cell –, and ensure that the Golgi apparatus remains functional. The researchers have just discovered that protein GMAP-210 acts as a "clamp", holding these future components of the Golgi apparatus close to the center of the cell to enable their assembly. To this end, the protein controls the formation of a short microtubule, which brings together and juxtaposes these pre-Golgi structures. The scientists have observed that the Golgi apparatus fragments when GMAP-210 is inactivated. In contrast, if GMAP-210 abounds, the Golgi grows ceaselessly and may even divide. It has therefore been shown that GMAP-210 plays an essential role in "maintaining" the Golgi apparatus and in positioning it in the center of the cell. Such upkeep and positioning are essential to the correct functioning of the cell, and on a larger scale to the organism as a whole. GMAP-210 was, moreover, identified because of its involvement in an auto-immune disease(4) and in certain leukemias.The Golgi apparatus is also "renewed" at each cell division from its own fragments, which presupposes a role for GMAP-210 in this crucial step (see box below).
The discovery of the key role of GMAP-210 heightens understanding of how the cell preserves its integrity throughout its life. Continued studies should cast light on other unsolved questions concerning the mechanisms indispensable to good functioning of the cell and indeed of the whole body.
Notes for editor Box"Marshalling yard" for proteins Located close to the centrosome, the Golgi apparatus is known above all for its stacks of flattened sacs or cisternae resembling a pile of pancakes. The number of cisternae varies hugely with cell type (from one to hundreds).The proteins synthesized in the endoplasmic reticulum are transported to the Golgi apparatus, where they are modified and sorted before being sent to other cellular compartments where they "accomplish their tasks". The Golgi apparatus acts as a "marshalling yard".
Cell division, the Golgi apparatus and protein GMAP-210…Cell division is a crucial stage in the life of a cell. To reproduce, the cell copies its essential components and then divides into two daughter cells. These inherit the genetic material and the organelles such as the endoplasmic reticulum, the Golgi apparatus... Each daughter cell inherits all the cellular machinery and must organize it. This calls for great reliability both in terms of the sharing of cellular components and their repositioning in the daughter cells. Ensuring this reliability is a challenge for the body as a whole, since at any given moment nearly 250 million cells are dividing. If the cell is to divide, then the Golgi apparatus must also divide. The daughter cells inherit fragments of the Golgi apparatus. These "little Golgi" return to their "post" near the centrosome by following the microtubule network. But the fragments must then be reassembled to reform the Golgi apparatus. In this crucial step in the cell’s life, protein GMAP-210 certainly plays a key role. Watch this space…
(1) Glossary: The endoplasmic reticulum is a tubular network which extends throughout the intracellular space, excepting the nucleus, like a three-dimensional spider’s web. It is the site of synthesis of membrane and soluble proteins.
The microtubules are oriented polymers that are assembled during the cell cycle from the centrosome and enable the transport of various organelles by molecular motors that can move in one direction or another.
The centrosome is the organizing center of the microtubules and is found in the middle of the cell.
(2) Michel Bornens is Director of Research at CNRS and heads the "Biology of cell cycle and cell motility" team within CNRS/Institut Curie unit UMR 144.
(3) Rosa Ríos, who was a post-doc in the group of Michel Bornens at the Institut Curie is currently directing this project at the Faculty of Biology at the University of Seville (Spain).
(4)Auto-immune diseases are characterized by the destruction of healthy cells, or even an organ, by the body’s own immune defenses.
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