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 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 event, mediated by changes at the cytoskeletal level, occurs at the leading edge of migrating cells? And, how would the indicated Rac-induced change in ARP2/3 activity in that region of the cells help facilitate this process?
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
Cytoskeletal frame work of the cell is responsible for the cell motility, contraction and movement of organelles and establishment of cell-polarity in the cells.
these tasks are accomplished through microfilaments and microtublins that are composed of ACTIN, TUBULINS respectively. These filaments and tubules are under the influence of proteins that regulate their length through cross-linking or polymerization.
Cell Polarity may be initiated spontaneously or in response to signaling inputs from adjacent cells or pathogenic activity or soluble factors and is stabilized by positive-feedback loops.
A conserved group of proteins, the Par proteins, plays a central role in polarity establishment and maintenance.
These proteins generate and maintain their distinct locations in cells by actively excluding one another from specific regions of the plasma membrane.
Arp2/3-mediated actin polymerisation and actomyosin contractility generate retrograde flow of F-actin,
which when engaged by a ‘clutch’ (focal adhesions) promotes traction force .
Formins can act as direct RhoGTPase effectors to polymerise and/or bundle F-actin from the barbed end,
and generate actin cables supporting the lamellipod area and force generation .
Polymerisation and bundling of a subset of linear actin filaments within needle-like protrusions forms a class of F actin-based protrusions broadly termed filopodia, and numerous pathways can lead to their formation.
These include convergent elongation from Arp2/3-generated dendritic actin networks, and direct polymerisation of actin from the barbed ends by formins, with critical supporting roles for Ena/VASP family members and actin-bundling
proteins.
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