Countless proteins perform specialized jobs within our bodies, and one of these is Sorting nexin 27, or SNX27. This protein operates deep within our cells, playing a part in maintaining cellular order and function. Its work is particularly important in the brain, and understanding its role provides insight into the processes that sustain health and what may happen when they are disrupted.
The Cellular World and Protein Sorting
Our bodies are composed of trillions of cells, each one a factory performing specific tasks. Inside these factories, proteins are the primary workers, built from genetic instructions to carry out nearly every function. For a cell to operate efficiently, these proteins must be delivered to the correct location at the correct time in a process called protein trafficking.
Think of this system as an internal postal service. A cell’s outer boundary, the plasma membrane, controls what comes in and out. When the cell takes in materials, it engulfs them into small bubbles called endosomes, which act as sorting stations. Here, incoming molecular packages are sorted; some are sent to be broken down by the lysosome, while others are sent back to the plasma membrane to be used again.
Introducing the Sorting Nexin Family
The task of sorting and trafficking proteins within the endosomal system is handled by a group of proteins called the Sorting Nexins, or SNX family. These proteins interact with the membranes of endosomes, helping to shape them and direct the flow of protein traffic. They act as coordinators, ensuring that the right cargo is sent to the right place.
Within this large family, SNX27 stands out due to its unique structure and functions. While all members of the SNX family can bind to endosomes, SNX27 possesses additional tools that give it a distinct role. It is particularly abundant in the brain, where precise protein trafficking supports communication between nerve cells and cognitive functions like learning and memory.
SNX27’s Unique Structure
The functions of SNX27 are dictated by its unique molecular architecture, composed of three main parts called domains. The first is the PX domain, a feature common to all SNX proteins, which acts as an anchor, allowing SNX27 to attach itself to the membranes of the endosomes.
What makes SNX27 special is its other two domains. It has a PDZ domain that functions like a grappling hook to catch specific targets. This domain recognizes and binds to “cargo” proteins, allowing SNX27 to selectively grab certain proteins that need to be recycled. Finally, its FERM domain acts as a connector, linking SNX27 and its captured cargo to a sorting complex known as the retromer.
This combination of domains allows SNX27 to perform its job with precision. It docks onto the endosome using its PX domain, grabs specific cargo with its PDZ domain, and uses its FERM domain to interface with the retromer complex. The retromer then helps package the cargo into new vesicles that are sent back to the cell surface for reuse.
The Role of SNX27 in Recycling
The primary function of SNX27 is to rescue and recycle transmembrane proteins. These are proteins embedded in the cell’s outer plasma membrane that act as channels and receptors, allowing the cell to communicate with its environment. Through its interaction with the retromer complex, SNX27 diverts these proteins away from the degradation pathway and directs them back to the cell surface.
This recycling process is especially active in the brain. Nerve cells, or neurons, communicate at junctions called synapses, and the strength of these connections can change over time in a process known as synaptic plasticity, the cellular basis for learning and memory. This plasticity depends on the number of receptors on the neuron’s surface, such as the AMPA and NMDA glutamate receptors. SNX27 recycles these glutamate receptors, ensuring they are available to receive signals and support cognitive function.
SNX27’s Connection to Disease
Given its role in protein recycling in the brain, malfunctions in SNX27 are linked to several human diseases. When SNX27 levels are low or the protein doesn’t work correctly, the recycling of its cargo proteins is impaired. This leads to a shortage of them on the cell surface, which can have significant consequences for cellular health.
In Down’s syndrome, a genetic condition caused by an extra copy of chromosome 21, individuals often have reduced levels of the SNX27 protein. A gene on chromosome 21 produces a molecule that suppresses SNX27 production. This shortage is thought to contribute to the learning and memory difficulties associated with the condition, as fewer glutamate receptors are recycled.
In Alzheimer’s disease, SNX27 levels have also been found to be reduced, which may affect the trafficking of proteins like the amyloid precursor protein (APP). Research has also begun to link SNX27 to certain cancers. In these cases, it may influence tumor growth by altering the trafficking of proteins involved in cell proliferation.