S100A10 - Function

Function

P11 is an integral part of cellular structural scaffolding that interacts with plasma membrane proteins through its association with annexin II. Recently, it was discovered to form a complex with annexin I though the mechanism remains unknown. It works together with cytosolic and peripheral membrane-associated proteins such as AHNAK in the development of the intracellular membrane. P11 has been implicated in the transportation of proteins involved in mood regulation, nociception, and cell polarization. It is found in cell types throughout the body though it is located predominantly in the lungs and kidneys. It is involved in the trafficking of proteins to the plasma membrane and can be expressed on the cell surface as a receptor. Many of the transported proteins are cell surface receptors in signal transduction pathways and ion channels. P11 facilitates nociception, Ca2+ uptake, and cell polaraization. Complexed with the annexin II, p11 binds receptor and channel proteins and guides them to the cell surface, resulting in increased membrane localization and consequent magnified functional expression of these proteins.

Ion channels are among the several proteins that are transported through the interaction with p11. Some of these proteins include Na_v1.8, TRPV5, TRPV6, TASK-1, and ASIC1a. Na_v1.8 is a tetrodotoxin-resistant sodium channel that replaces lost sodium after cell damage. Increased expression of these channels alters the magnitude of the sodium current across the membrane. TRPV5 and TRPV6 are transient receptor potential channels selective for Ca+ and Mg2+ ions. TASK-1 is a two-pore domain K+ channel TWIK-related acid-sensitive K (TASK). P11 can also function as a retention factor, preventing TASK-1 from leaving the endoplasmic reticulum. ASIC1a is an acid-sensing ion channel involved in the pain sensory pathway, which is regulated by p11.

Although the exact mechanism is unclear, p11 protein has shown to be essential in the regulation of serotonin signaling in the brain. Serotonin (5-hydroxytryptamine or 5-HT), is a neurotransmitter found in the central and peripheral nervous systems. It is involved in mechanisms responsible for memory formation and learning, but is most known for its role in the regulation muscle contraction, appetite, sleep, and mood. Varying levels of serotonin found in the brain are associated with the development of mood disorders, such as clinical depression. P11 interacts with the serotonin receptor proteins, 5-HT receptors such as 5-HT_1B, modulating the receptor signal transduction pathways activated by the binding of serotonin. P11 also recruits the cell surface expression of the 5-HT₄ receptor, increasing its concentration at the synapse. This results in more rapid serotonin-dependent activities. 5-HT₄ is involved in the regulation of kinase activity in the central nervous system, phosphorylating target proteins, and facilitating endosomal activities. P11 is coexpressed with 5-HT₄ mRNA and its protein in parts of the brain associated with depression, suggesting that their functions are linked and influence mood.

Protein p11 can also be presented on the cell surface as a receptor for tissue-type plasminogen activator (tPA) and plasminogen. Plasmin production by many cells is dependent on p11.