Amoeboid cells that migrate through our tissues, such as the class of white blood cells known as neutrophils, often do so in a directed manner, triggered, for instance, by chemical signals released by pathogens such as bacteria. Directed migration in response to a chemical stimulus is known as chemotaxis. Part of an efficient chemotactic response is the ability of cells to polarize. As is the case with our structurally-polar polymers like F-actin or microtubules, polarization here refers to an asymmetry in the cells, rather than an electrical charge. In this case, it involves one part of the cell becoming the “front” (or leading edge) and another the rear. In a well-polarized, migrating cell, it’s been observed that an active form of Rac (which, in turn, can activate ARP 2/3) is concentrated towards the front of the cell, whereas an active form of Rho (which, in turn, can activate formin, inhibit cofilin/ADP, and activate myosin II) is found toward the rear of the cell. Based on your understanding of the events involved in amoeboid cell movement, and the role of these various actin-associated proteins what common mechanism (specifically a change in an associated molecule) is used to activate both Rac and Rho?
Amoeboid cells that migrate through our tissues, such as the class of white blood cells known as neutrophils, often do so in a directed manner, triggered, for instance, by chemical signals released by pathogens such as bacteria. Directed migration in response to a chemical stimulus is known as
RAC is responsible for protrusion as well as attachment and thus, dominates at the leading edge while Rho will dominate at the trailing edge because it is used for traction. These three steps, protrusion, attachment and traction, are important for cell movement.
During the process of chemotaxis, the binding of a chemoattractant will lead to the activation of both Rac and Rho at the leading edge and trailing edge, respectively.
When Rac is activated, it will work by promoting the actin polymerization, which will result in the formation or production of lamellipodia, which is important for whole cell locomotion. This actin polymerization will lead to the protrusion, which will allow directional cell movement, as actin filaments will extend outward in the moving direction. In this case, it is towards the chemoattractant.
When Rho is activated, it will work by facilitating stress fiber formation, and better contraction through myosin. This is required for the traction step taking place during cell movement. It occurs at the trailing edge to facilitate directional cell movement due to resulting in actin-myosin contractions, therefore moving the trailing edge of the cell in the forward direction.
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