Neurofilaments: Axons of neurons, imparting strength and rigidity
Glial fibrillary acidic protein: Glial cells that support neurons
Cytokeratins: Epithelial cells express more than 30 distinct varieties with distinct patterns of expression in different lineages (e.g., lung versus gastrointestinal epithelia). These can serve as histochemical markers for various epithelia Intermediate filaments are found predominantly in a ropelike polymerized form and primarily serve to impart tensile strength and allow cells to bear mechanical stress. The nuclear membrane lamins are important not only for maintaining nuclear morphology but also for regulating nuclear gene transcription. The critical roles of lamins is emphasized by rare but fascinating disorders caused by lamin mutations, which range from certain forms of muscular dystrophy to progeria, a disease of premature aging. Intermediate filaments also form the major structural proteins of epidermis and hair.
Microtubules are 25-nm-thick fibrils composed of noncovalently polymerized dimers of α-and β-tubulin arrayed in constantly elongating or shrinking hollow tubes with a defined polarity; the ends are designated “+” or “−.” The “−” end is typically embedded in a microtubule organizing center (MTOC or centrosome) near the nucleus where it is associated with paired centrioles, while the “+” end elongates or recedes in response to various stimuli by the addition or subtraction of tubulin dimers. Microtubules are involved in several important cellular functions:
Support cables for “molecular motor” proteins that allow the movement of vesicles and organelles around cells. Kinesins are the motors for anterograde (− to +) transport, whereas dyneins move cargo in a retrograde direction (+ to −).
The mechanical support for sister chromatid separation during mitosis
The core of primary cilia, single nonmotile projections on nucleated cells that help regulate proliferation and differentiation
The core of motile cilia (e.g., in bronchial epithelium) or flagella (in sperm)
Cells interact and communicate with one another by forming junctions that provide mechanical links and enable surface receptors to recognize ligands on other cells. Cell junctions are organized into three basic types (
Fig. 1.9
Occluding junctions (tight junctions) seal adjacent cells together to create a continuous barrier that restricts the paracellular (between cells) movement of ions and other molecules. Viewed en face, occluding junctions form a tight meshlike network of macromolecular contacts between neighboring cells. The complexes that mediate these cell–cell interactions are composed of multiple proteins, including occludin and claudin. In addition to being a high-resistance barrier to solute movement, occluding junctions also maintain cellular polarity by forming the boundary between apical and basolateral domains of cells. Significantly, these junctions (as well as the desmosomes described later) are dynamic structures that can dissociate and reform as required to facilitate epithelial proliferation or inflammatory cell migration.
Anchoring junctions (desmosomes) mechanically attach cells—and their intracellular cytoskeletons—to other cells or to the ECM. When the adhesion focus is between cells, and is small and rivetlike, it is designated a spot desmosome. When such a focus attaches the cell to the ECM, it is called a hemidesmosome. Similar adhesion domains can also occur as broad bands between cells, where they are denoted as belt desmosomes. Cell–cell desmosomal junctions are formed by the homotypic association of transmembrane glycoproteins called cadherins.
In spot desmosomes, the cadherins are linked to intracellular intermediate filaments and allow extracellular forces to be mechanically communicated (and dissipated) over multiple cells.
In belt desmosomes, the transmembrane adhesion molecules are associated with intracellular actin microfilaments, by which they can influence cell shape and/or motility.