Cell polarity

Cells are not uniform inside—they have distinct regions with different shapes, structures, and jobs. This is called cell polarity, and nearly every cell type has it. Polarity lets cells perform specialized tasks. Classic examples include epithelial cells, which have an apical (top) and basolateral (bottom) side; neurons, which send signals in one direction from dendrites to axons; and migrating cells, which have a clear front and rear. Polarity also matters during asymmetric cell division, where daughter cells end up with different functions.

Many of the key molecules behind polarity are similar across species. In animals, a complex made of PAR-3, PAR-6, and aPKC is central. Although the exact biochemical details differ, common principles—like positive and negative feedback between molecules—are essential for most polarity systems.

**Examples of polarized cells**

**Epithelial cells** These cells stick together using tight junctions, desmosomes, and adherens junctions, forming sheets that line body surfaces and internal cavities (like the gut or blood vessels). They have apical-basal polarity: the apical membrane faces the outside or the cavity's lumen, while the basolateral membrane faces away. The basolateral side includes both the lateral membrane (where cells connect to neighbors) and the basal membrane (attached to the basement membrane, a thin layer of extracellular matrix separating the sheet from underlying tissue). Epithelial cells also show planar cell polarity, where structures line up within the sheet's plane—for example, fish scales, bird feathers, mammal fur, and insect sensory hairs all point in the same direction. Computer models have been used to simulate how groups of epithelial cells create various biological shapes.

**Neurons** A neuron receives signals from other cells through branched extensions called dendrites. It then sends an electrical signal down a specialized axon from its base to the synapse, where neurotransmitters are released to pass the signal to another neuron or an effector cell (like a muscle or gland). This polarity ensures information flows in one direction, which is essential for communication between neurons and other cells.

**Migratory cells** Many cell types, such as leukocytes and fibroblasts, can move. To travel in one direction, they need a defined front and rear. At the front is the leading edge, often marked by a flat, ruffling membrane called a lamellipodium or thin projections called filopodia. Here, actin polymerization pushes the membrane forward and helps the cell attach to the surface. At the rear, adhesions break down, and bundles of actin called stress fibers contract, pulling the trailing edge forward. Without this front-rear polarity, directed migration would be impossible.

**Budding yeast** The budding yeast *Saccharomyces cerevisiae* is a model for studying polarity. It shares many polarity features with other organisms but has fewer components. Polarity usually starts at an inherited landmark—a patch of the protein Rsr1 for budding, or Rax1 for mating projections. If these landmarks are missing (in gene deletion mutants), cells can spontaneously break symmetry, choosing a random spot for polarity. Even then, only one bud site forms, thanks to positive feedback that boosts polarity proteins at the largest patch while depleting them elsewhere. The master regulator is Cdc42, a Rho-family GTPase (related to Rop GTPases in plants and small GTPases in bacteria). For polarity sites to form, Cdc42 must be present and able to cycle GTP, controlled by its activator Cdc24 (a GEF) and its inhibitors (GAPs). Cdc42's location is also regulated by cell cycle cues and various binding partners. One recent study used optogenetics (controlling protein location with light) to link cell cycle timing to Cdc42 buildup at the bud site. During mating, polarity sites can move, and experiments combined with mathematical modeling suggest this relocation relies on actin-driven vesicle delivery.

**Vertebrate development** Vertebrate bodies are asymmetric along three axes: front-to-back (head to tail), top-to-bottom (spine to belly), and left-right (e.g., the heart on the left). These polarities arise in the embryo through several processes: (1) asymmetric cell division, where daughter cells get different amounts of materials like mRNA or proteins; (2) asymmetric placement of specific proteins or RNAs inside cells, often guided by the cytoskeleton; and (3) concentration gradients of secreted proteins across the embryo.