Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

CELL POLARIZATION AND MIGRATION
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CELL POLARIZATION AND MIGRATION
A central challenge in cell biology is to understand how multiple individual
molecular components collaborate to produce complex cell behaviors. The process
of cell migration, which we describe in this final section, relies on the coordinated
deployment of the components and processes that we have explored in
this chapter: the dynamic assembly and disassembly of cytoskeletal polymers, the
regulation and modification of their structure by polymer-associated proteins,
and the actions of motor proteins moving along the polymers or exerting tension
against them. How does the cell coordinate all these activities to define its polarity
and enable it to crawl?
Many Cells Can Crawl Across a Solid Substratum
Many cells move by crawling over surfaces rather than by using cilia or flagella
to swim. Predatory amoebae crawl continuously in search of food, and they can
easily be observed to attack and devour smaller ciliates and flagellates in a drop
of pond water (see Movie 1.4). In animals, almost all cell locomotion occurs by
crawling, with the notable exception of swimming sperm. During embryogenesis,
the structure of an animal is created by the migrations of individual cells to
specific target locations and by the coordinated movements of whole epithelial
sheets (discussed in Chapter 21). In vertebrates, neural crest cells are remarkable
for their long-distance migrations from their site of origin in the neural tube to a
variety of sites throughout the embryo (see Movie 21.5). Long-distance crawling
is fundamental to the construction of the entire nervous system: it is in this way
that the actin-rich growth cones at the advancing tips of developing axons travel
to their eventual synaptic targets, guided by combinations of soluble signals and
signals bound to cell surfaces and extracellular matrix along the way.
The adult animal also seethes with crawling cells. Macrophages and neutrophils
crawl to sites of infection and engulf foreign invaders as a critical part of
the innate immune response. Osteoclasts tunnel into bone, forming channels that
are filled in by the osteoblasts that follow after them, in a continuous process of
bone remodeling and renewal. Similarly, fibroblasts migrate through connective
tissues, remodeling them where necessary and helping to rebuild damaged structures
at sites of injury. In an ordered procession, the cells in the epithelial lining
of the intestine travel up the sides of the intestinal villi, replacing absorptive cells
lost at the tip of the villus. Unfortunately, cell crawling also has a role in many
cancers, when cells in a primary tumor invade neighboring tissues and crawl into
blood vessels or lymph vessels and then emerge at other sites in the body to form
metastases.
Cell migration is a complex process that depends on the actin-rich cortex
beneath the plasma membrane. Three distinct activities are involved: protrusion,
in which the plasma membrane is pushed out at the front of the cell; attachment,
in which the actin cytoskeleton connects across the plasma membrane to the substratum;
and traction, in which the bulk of the trailing cytoplasm is drawn forward
(Figure 16–75). In some crawling cells, such as keratocytes from the fish epidermis,
these activities occur simultaneously, and the cells seem to glide forward
smoothly without changing shape. In other cells, such as fibroblasts, these activities
are more independent, and the locomotion is jerky and irregular.
Actin Polymerization Drives Plasma Membrane Protrusion
The first step in locomotion, protrusion of a leading edge, frequently relies on
forces generated by actin polymerization pushing the plasma membrane outward.
Different cell types generate different types of protrusive structures, including
filopodia (also known as microspikes) and lamellipodia. These are filled with
dense cores of filamentous actin, which excludes membrane-enclosed organelles.
The structures differ primarily in the way in which the actin is organized by
actin-cross-linking proteins (see Figure 16–22).