麻豆淫院

Symmetry is a fundamental characteristic of most multi-cell animals. However, the cell division of embryonic cells is asymmetric. A team led by Prof. Dr. Esther Zanin at the Department of Biology at Friedrich-Alexander-Universit盲t Erlangen-N眉rnberg (FAU) has developed a working model that explains the molecular mechanism with which the protein anillin controls asymmetry during the constriction of the parent cell. Since large amounts of anillin are found in tumor cells, the suspected mechanism could open the door to new types of cancer treatments.

The paper is in the Journal of Cell Biology.

Cell division can be observed live under an optical microscope. At the beginning of the process, a ring made of thread-like actin proteins forms at the equator of the parent cell and constricts symmetrically.

As the process continues, the ring becomes asymmetrical, which means it contracts more strongly at one point than at the opposite end. The diameter of the ring continues to shrink until the separation of the parent cell is complete.

Until now, researchers did not know what triggers the asymmetry of the ring. What was known is that the process is controlled by the mechanical flow movement of the actin fibers and the protein anillin. Without the influence of anillin, the ring contracts symmetrically.

Embryos of a nematode

In Prof. Zanin's lab at the Professorship for Experimental Molecular Cell Dynamics at FAU, the first cell division of embryos of the nematode Caenorhabditis elegans is being investigated. While it is possible to photograph the cells, which are 50 thousandths of a millimeter (渭m) long and 20 渭m wide, the images from the optical microscope are not of sufficient quality to enable the process to be observed at the molecular level. However, it is possible to mark components of the contractile ring with fluorescent proteins, thus making them visible under a fluorescence microscope.

In the nematode embryo, Mikhail Lebedev, lead author of the study, generated genetically modified mutations of anillin (which comprises 1159 amino acids) where the docking regions of the protein were modified. The cell division process of each protein variant and the constricting of the ring was documented with photographs every 15 seconds.

The researchers discovered that there are two regions (domains) on the large molecule that influence the ring asymmetry: a spherical folded (globular) domain and a very flexible region of unfolded amino acid strands.

The ring constricts when its actin fibers mesh into each other under the influence of the "motor protein" myosin. Myosin itself must be activated by an active variant of the switching protein RhoA to enable it to fulfill its function as a motor. The switching protein has a region that can switch between two different states, where the active form activates myosin and the inactive form does not.

Switch is blocked by anillin

Prof. Zanin's team has now been able to demonstrate that anillin does not influence the switching function of RhoA, but simply makes the active form of the switch inaccessible. When the globular domain of anillin docks onto the active RhoA switching protein, it prevents other proteins from binding and the "motor" myosin remains inactive. This binding is intensified further by the flexible region of the anillin. Both phenomena lead to a slowing down of the contraction on one side of the ring and thus to asymmetry.

The globular and flexible regions of the anillin molecules evidently both influence the ring asymmetry. Prof. Zanin's team suspect that the flexible region of the anillin "detects" the mechanical currents of the actin fibers in some way and adapts the binding capacity of the globular domain.

Strong currents create a weak bond between the spherical domain of anillin to RhoA, which means the the switch is "on", the myosin motor protein is activated and the ring in this area contracts more strongly than on the opposite end. This inevitably leads to asymmetry.

In contrast, weak currents create strong bonds with RhoA, which weakens the contractions. The flow speed of the actin fibers evidently has a major influence on the asymmetry of the constricting ring. How the flexible region of the anillin protein "detects" this current and passes this information on to the spherical domain will be the subject of further basic research.

The shared ancestry of all animals has led to the observation that asymmetric constriction of the ring does not only occur in nematodes, but also in human skin cells. This means that this research could be important for our understanding of the protective function of human skin or the containment of tumor cells, for example.