Cell polarity
Introduction
Cell polarity refers to the spatial differences in the shape, structure, and function of cells. This phenomenon is essential for numerous biological processes, including cell differentiation, cell migration, and the formation of tissues and organs. Cell polarity is a fundamental aspect of cellular organization and is critical for the proper functioning of multicellular organisms.
Types of Cell Polarity
Apical-Basal Polarity
Apical-basal polarity is a type of cell polarity observed in epithelial cells, which line the surfaces and cavities of organs. These cells have distinct apical (top) and basal (bottom) surfaces, each with specific functions and molecular compositions. The apical surface often faces the lumen or external environment and is involved in absorption and secretion, while the basal surface interacts with the underlying basement membrane and connective tissue.
Planar Cell Polarity
Planar cell polarity (PCP) refers to the coordinated orientation of cells within the plane of a tissue. This type of polarity is crucial for processes such as the alignment of hair cells in the inner ear and the directional movement of cilia on epithelial surfaces. PCP is regulated by a set of conserved signaling pathways, including the Wnt/PCP pathway.
Front-Back Polarity
Front-back polarity, also known as anterior-posterior polarity, is observed in migrating cells. This type of polarity involves the formation of a leading edge (front) and a trailing edge (back), allowing cells to move directionally. Key components of front-back polarity include the actin cytoskeleton, microtubules, and signaling molecules such as Rho GTPases.
Molecular Mechanisms of Cell Polarity
Polarity Complexes
Cell polarity is established and maintained by several conserved protein complexes, including the Par complex, the Crumbs complex, and the Scribble complex. These complexes interact with each other and with the cytoskeleton to define distinct cellular domains.
Par Complex
The Par complex consists of Par3, Par6, and atypical protein kinase C (aPKC). This complex is crucial for establishing apical-basal polarity in epithelial cells. Par3 acts as a scaffold protein, recruiting Par6 and aPKC to the apical membrane, where they regulate the assembly of tight junctions and the segregation of apical and basal domains.
Crumbs Complex
The Crumbs complex includes the transmembrane protein Crumbs, the cytoplasmic protein PALS1, and the adaptor protein PATJ. This complex is involved in maintaining apical membrane identity and regulating cell-cell adhesion. Crumbs interacts with other apical proteins to stabilize the apical domain and prevent the expansion of the basal domain.
Scribble Complex
The Scribble complex comprises Scribble, Discs large (Dlg), and Lethal giant larvae (Lgl). This complex is essential for establishing basolateral identity and regulating cell proliferation and differentiation. Scribble interacts with Dlg and Lgl to promote the formation of adherens junctions and the segregation of basolateral proteins.
Cytoskeleton
The cytoskeleton, composed of actin filaments, microtubules, and intermediate filaments, plays a crucial role in cell polarity. Actin filaments are involved in the formation of cellular protrusions and the establishment of front-back polarity. Microtubules provide structural support and serve as tracks for the transport of polarity proteins and organelles. Intermediate filaments contribute to the mechanical stability of polarized cells.
Regulation of Cell Polarity
Signaling Pathways
Several signaling pathways regulate cell polarity, including the Wnt, Hedgehog, and Notch pathways. These pathways modulate the activity of polarity complexes and the cytoskeleton to coordinate the establishment and maintenance of polarity.
Wnt Pathway
The Wnt pathway is involved in planar cell polarity and apical-basal polarity. Wnt signaling regulates the localization and activity of polarity proteins, such as Dishevelled and Frizzled, which are essential for the establishment of PCP.
Hedgehog Pathway
The Hedgehog pathway plays a role in the regulation of cell polarity during development. Hedgehog signaling influences the distribution of polarity proteins and the organization of the cytoskeleton, contributing to the formation of polarized tissues and organs.
Notch Pathway
The Notch pathway is involved in cell fate determination and the regulation of cell polarity. Notch signaling modulates the expression of polarity proteins and the organization of cell junctions, influencing the establishment of apical-basal polarity in epithelial cells.
Extracellular Cues
Extracellular cues, such as cell-cell interactions and the extracellular matrix (ECM), also play a critical role in the regulation of cell polarity. Cell-cell interactions mediated by adhesion molecules, such as cadherins and integrins, provide spatial information that guides the establishment of polarity. The ECM provides structural support and biochemical signals that influence cell polarity and behavior.
Functional Significance of Cell Polarity
Tissue Organization
Cell polarity is essential for the organization and function of tissues. In epithelial tissues, apical-basal polarity allows for the formation of barriers and the selective transport of molecules. In neural tissues, polarity is crucial for the formation of axons and dendrites, which are necessary for the transmission of nerve impulses.
Cell Migration
Cell polarity is a key determinant of cell migration, which is important for processes such as wound healing, immune response, and embryonic development. The establishment of front-back polarity allows cells to move directionally in response to external signals, such as chemokines and growth factors.
Asymmetric Cell Division
Asymmetric cell division, in which a parent cell divides to produce two daughter cells with distinct fates, relies on cell polarity. Polarity cues ensure the unequal distribution of cell fate determinants, leading to the generation of diverse cell types during development and tissue homeostasis.
Pathological Implications of Cell Polarity
Cancer
Disruption of cell polarity is a hallmark of cancer. Loss of polarity can lead to uncontrolled cell proliferation, invasion, and metastasis. Mutations in polarity genes, such as those encoding Par, Crumbs, and Scribble complex proteins, have been implicated in the development of various cancers.
Developmental Disorders
Defects in cell polarity can result in developmental disorders, such as neural tube defects and polycystic kidney disease. These disorders arise from the improper organization of cells and tissues, leading to structural abnormalities and impaired function.
Neurodegenerative Diseases
Cell polarity is also implicated in neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease. Disruption of neuronal polarity can lead to the mislocalization of proteins and organelles, contributing to the degeneration of neurons and the progression of these diseases.
Research Techniques for Studying Cell Polarity
Microscopy
Microscopy techniques, such as confocal microscopy and electron microscopy, are widely used to study cell polarity. These techniques allow for the visualization of cellular structures and the localization of polarity proteins with high resolution.
Molecular Biology
Molecular biology techniques, such as gene knockdown and overexpression, are used to investigate the function of polarity proteins. These techniques involve the manipulation of gene expression to study the effects on cell polarity and behavior.
Biochemical Assays
Biochemical assays, such as co-immunoprecipitation and Western blotting, are employed to study the interactions between polarity proteins. These assays provide insights into the molecular mechanisms underlying the establishment and maintenance of cell polarity.
Genetic Models
Genetic models, such as Drosophila and mice, are used to study cell polarity in vivo. These models allow for the investigation of the role of polarity genes in development and disease, providing valuable insights into the physiological relevance of cell polarity.