Cell polarity is a fundamental principle describing the inherent asymmetry within a cell. This means a cell’s internal components, membrane surfaces, and overall architecture are distinctly organized along a defined axis. A cell is not a uniform bag of molecules but a highly structured entity where different regions are specialized to perform specific tasks. This directionality allows cells to execute complex, coordinated functions necessary for the survival and proper functioning of multicellular organisms.
Structural Basis of Cellular Organization
Cell polarity is clearly demonstrated in epithelial cells, which form protective sheets lining surfaces like the skin, gut, and internal organs. These cells organize along the apical-basolateral axis. The apical domain faces the external environment or a body lumen, while the basal domain rests on the basement membrane, connecting the cell to the underlying tissue. The lateral domains connect neighboring cells, forming a cohesive tissue barrier.
Each membrane domain has a unique protein and lipid composition that dictates its function. The apical domain is often specialized for absorption or secretion, containing structures like microvilli or cilia. The basal domain is specialized for communication with the surrounding tissue and the bloodstream.
A physical barrier called the tight junction encircles the cell near the apical surface. It acts as a fence to maintain the distinct identities of the apical and basolateral membranes by preventing the free diffusion of membrane proteins and lipids. Tight junctions also control the movement of molecules between cells (paracellular permeability), which is essential for the body’s barrier function.
Molecular Mechanisms of Asymmetry
The establishment of precise asymmetry is orchestrated by highly conserved molecular machinery. Polarity is maintained through the coordinated interplay of three main protein complexes: the PAR, Crumbs, and Scribble complexes. These complexes are strategically positioned and work in mutual antagonism to partition the cell into distinct domains.
The PAR and Crumbs complexes are primarily localized to the apical domain. The PAR complex, consisting of proteins like Par-3, Par-6, and atypical protein kinase C (aPKC), initiates the polarization process. The Crumbs complex acts as an apical determinant, helping establish and maintain the boundaries of the apical surface.
Conversely, the Scribble complex, composed of Scribble, Discs large, and Lethal giant larvae, is localized to the basolateral domain. The components of the apical complexes actively inhibit the basolateral complex components, and vice versa. This mutual exclusion creates a sharp boundary that ensures the robust separation of cellular functions.
The cell’s internal scaffolding, the cytoskeleton, is also involved in enforcing this directionality. Microtubules and actin filaments act as highways and anchoring points for the transport and retention of specific components. The precise delivery and anchoring of polarity proteins depend on the cytoskeleton, which physically reinforces the molecular decisions made by the polarity complexes.
Essential Roles in Tissue Function
The directionality provided by cell polarity is functionally indispensable for numerous biological processes.
Directional Transport
One prominent role is in directional transport, where distinct apical and basolateral surfaces allow for the selective movement of substances across tissue layers. In the gut and kidney, nutrients and ions are absorbed from the apical side and then efficiently transported into the bloodstream via the basal side.
Cell Migration
Polarity is fundamental to the process of cell migration, which is necessary for wound healing, immune response, and development. Migrating cells establish a front-to-back polarity, creating a leading edge for movement and a trailing edge for retraction. This internal organization guides the cell’s movement in response to external signals.
Morphogenesis
During embryonic development, cell polarity is a defining factor in morphogenesis, the process by which tissues and organs acquire their shape. Polarity dictates how cells arrange themselves to form layered structures, hollow tubes, and complex organ architectures. Without this precise directionality, tissues would fail to layer correctly, leading to severe developmental defects.
Asymmetric Cell Division
Polarity governs asymmetric cell division, where a mother cell divides to produce two daughter cells with different fates. By partitioning specific proteins or determinants unequally, polarity ensures that one daughter cell becomes a stem cell while the other differentiates into a specialized cell type. This mechanism is crucial for maintaining tissue homeostasis.
Impact of Polarity Defects on Health
When mechanisms that maintain cell polarity fail, the consequences can lead to various diseases. The most studied link is between the loss of polarity and the development of cancer. Epithelial cells that lose directionality often undergo epithelial-to-mesenchymal transition (EMT).
This loss of organization is a hallmark of metastatic cancer, allowing cells to detach from the primary tumor and migrate to distant sites. Polarity proteins, particularly those in the Scribble complex, function as tumor suppressors, and their loss is frequently observed in human cancers. Disruption of apical-basal polarity promotes cell invasion and the aggressive behavior characteristic of malignant tumors.
Defects in polarity machinery are also implicated in other specific organ diseases. Mutations in components of the Crumbs complex have been linked to retinal degeneration. Disruptions in the planar cell polarity pathway can contribute to the formation of cysts in conditions like polycystic kidney disease.