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News DetailsMax Planck researchers in Dresden focus on the physics of PAR protein motion EMBARGOED! Cell polarity is a term used to describe a number of cellular pathways that allow cells to orient along a geometric axis. A key step in this process is the segregation of two groups of highly conserved PAR polarity proteins, first discovered in the nematode C. elegans, into two complementary membrane-associated domains. The domains mark the anterior and posterior halves of the cell and the different PAR proteins within these two domains spatially regulate a series of downstream pathways that reorganize the cell along this axis. As it turns out, the same basic polarity machinery that underlies polarity in the early embryo, also governs developmental processes through higher animals, including tissue architecture in the intestine, skin, and brain, and the regulation of cell fate decisions such as whether stem cells proliferate or differentiate. Thus, perhaps not surprisingly, defects in polarity are associated with severe developmental defects and cancer. (Science, 20 October 2011) Stephan Grill is a wanderer between two Dresden Max Planck Institutes: He is located both at the one for Molecular Cell Biology and Genetics and the one for Physics of Complex Systems. Thus, his research projects always bring physics into biology - or the other way round. Recently, his team was interested in the biological phenomenon of how polarity emerges in an embryo - and moved beyond trying to understand the detailed molecular activities of proteins, and instead focused on the physics of the problem, taking into account PAR protein motion and the forces that PAR proteins experience as they move through the embryo. Previous work had shown that two groups of PAR proteins, one "anterior" and one "posterior", were able to antagonize one another at the membrane, and that the initial segregation of PAR proteins was induced by the directed motion of a thin layer of a contractile actin meshwork that lies just under the cell membrane, which seemed to carry the "anterior" group of PAR proteins preferentially to the anterior of the cell, with the other group coming to occupy the "posterior." But how this all worked was really unclear. The current studies revealed that this actin-based fluid flow is sufficient to cause the polarized segregation of PAR proteins simply by virtue of PAR proteins being entrained within this thin layer of fluid just beneath the membrane. This phenomenon, which is called advection, is the same process that governs the spread of particles in the ocean: "Like a message in a bottle being The second key question was why the segregation by flow results in the formation of two domains that persist once flows cease. One group of PAR proteins is initially on the membrane and keeps the other off. This pattern (or lack of pattern) is stable until flows start. Once the first group gets pushed to the anterior, the other can come onto the membrane in the posterior. Once both are on the membrane, the interactions maintain the new polarized pattern. „We actually like this model a lot", says Nathan Goehring, "because it can, based on only a few simple ingredients and physical principles, explain quite a few of the key features of embryo polarization". There are a lot of answered questions, including how PAR proteins are able to associate with the membrane, or how they "talk" to each other in molecular terms. No problem for Goehring: "This open-ended nature of the polarity problem is actually quite good for a relatively young scientist such as myself". Caption: |
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