What Are Par Proteins and Why Are They Important?

Par proteins are a group of proteins found across the animal kingdom that serve as regulators of a cell’s internal architecture. Their primary responsibility is to organize components within a cell, establishing a sense of direction and order. This internal organization allows cells to perform specialized functions and build complex tissues. They create landmarks within the cell, guiding the placement of other structures, which allows a single, uniform cell to develop distinct regions for specific tasks.

The Core Function of Establishing Cell Polarity

The primary function of Par proteins is establishing cell polarity, which gives a cell distinct “top” and “bottom” or “front” and “back” regions. This process begins when Par proteins form a complex that anchors to one side of the cell cortex, the layer just beneath the cell membrane. This initial landmark serves as a command post for the cell’s internal machinery.

This core group, called the Par complex, includes proteins like PAR-3, PAR-6, and an enzyme called atypical Protein Kinase C (aPKC). Once this complex assembles at a specific location, it actively prevents a second set of Par proteins from localizing to the same area. For instance, in the early embryo of the worm C. elegans, the “anterior” Par complex at one end causes “posterior” Par proteins to accumulate at the opposite end.

This mutual exclusion creates two distinct domains. The establishment of these domains influences the organization of the cell’s internal skeleton, the cytoskeleton, and directs the transport of organelles and other molecules. The system is also dynamic, allowing the cell to respond to external cues and adapt its internal organization.

Directing Asymmetric Cell Division

The polarity established by Par proteins is directly linked to asymmetric cell division. This process allows a single parent cell to produce two daughter cells with different identities and futures. For example, one daughter cell might remain a stem cell while the other becomes specialized. This mechanism enables a single fertilized egg to generate the vast diversity of cell types in an organism.

The process relies on the segregation of molecules known as cell fate determinants. Guided by the landmarks set by Par proteins, these determinants are moved to one side of the parent cell before it divides. When the cell splits, only one of the new cells inherits this molecular cargo, setting the two cells on distinct developmental paths.

The discovery of Par proteins came from studying this process in the nematode worm, C. elegans. Scientists observed that mutations in “par” genes disrupted the first division of the worm embryo, which produces one larger and one smaller cell with different fates. This research revealed how Par proteins create the initial anterior-posterior (front-back) axis, ensuring developmental factors are correctly partitioned.

Maintaining Structure in Specialized Tissues

Par protein activity continues in adult tissues, where they maintain the specialized organization of cells. This is evident in epithelial tissues, which form the linings of organs and our skin. In these tissues, Par proteins establish and preserve the distinct apical and basolateral surfaces of each cell.

The apical surface faces an external space, like the inside of the intestine, while the basolateral surface connects to underlying tissues. Par proteins define the boundary between these domains, allowing the cell to perform directional tasks. For example, a cell can absorb nutrients on its apical side and pass them into the bloodstream on its basolateral side. This polarity enables epithelial sheets to form selective barriers.

The nervous system also demonstrates the importance of Par proteins. A neuron’s function depends on its polarized structure. Par proteins are involved in specifying one cellular extension as the axon, which transmits signals, and the others as dendrites, which receive them. This structural organization makes neural communication possible.

Connection to Cancer and Developmental Disorders

Disruption of Par protein function can have severe consequences. A loss of the cell polarity they control is a feature of many cancers, as the well-defined structure in healthy tissues helps keep cell growth in check. When cells lose their polarity, this organization breaks down, contributing to the uncontrolled proliferation that characterizes tumor formation.

This loss of structure is also relevant to cancer metastasis. When epithelial cells lose their apical-basal polarity, the tissue barrier is compromised. This breakdown allows cancerous cells to detach from the primary tumor, invade surrounding tissues, and travel to distant sites. The malfunction of Par proteins is often observed in aggressive cancers.

Errors in Par protein function can also lead to developmental disorders. Because these proteins direct asymmetric cell division, mutations in their genes can disrupt the earliest stages of tissue and organ formation. This can interfere with the generation of diverse cell types and the proper construction of complex structures, leading to a range of congenital conditions.