In addition, due to its interaction with serotonin-signaling proteins and its correlation with symptoms of mood disorders, p11 is a new potential target for drug therapy.

Proteins in the S100 gene family are known to regulate a number of cellular processes, such as cell cycle progression and differentiation.

[9] The p11 protein can be found as a free monomer, a homodimer, or a heterotetramer composed of a p11 dimer complex with two molecules of annexin II.

The dimerized form of the protein is created by packing between the H1 and H4 helices in an antiparallel arrangement with the hydrophobic regions residing in the core.

The EF-hand types, united by an anti-parallel beta-strand between loops L1 and L3, are located on the same side of the molecule, opposite the N-and C-termini.

This tetrameric complex is more stable than the p11 dimer, therefore the overexpression of the annexin II gene results in higher levels of p11 protein.

[11][12] P11 is an integral part of cellular structural scaffolding that interacts with plasma membrane proteins through its association with annexin II.

It is involved in mechanisms responsible for memory formation and learning, but is most known for its role in the regulation of muscle contraction, appetite, sleep, and mood.

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.

[13] Current experiments on animals have shown that various factors and physiological stimuli have been successful in regulating the levels of p11 protein transcription.

Very little is known about the underlying pathophysiology of clinical depression and other related mood-disorders including anxiety, bipolar disorder, ADD, ADHD, and schizophrenia.

Knockout experiments in which the gene coding for protein p11 was deleted from the mouse genome caused them to show signs of depression.

When mice that showed depressive symptoms were administered anti-depressant drugs, their levels of p11 were found to increase at the same rate, as antidepressants affected their behavioral changes.

In addition, post-mortem comparisons of brain tissues showed much lower levels of p11 in depressed compared to control subjects.

On the other hand, when p11 levels decrease, fewer 5-HT1B receptors migrate from inside the neuron to the cell membrane at the synaptic cleft, thus lowering the efficiency with which serotonin signaling can occur across the synapse.

These findings suggest that, although the serotonin levels are immediately introduced via medication, the period of time within which the medicine alleviates the patient's depression most likely relies on other regulatory proteins.

[37] Treatment with antidepressants (a tricyclic and monoamine oxidase inhibitor) and electroconvulsive therapy (ECT) caused an increase in the amount of p11 in the brain of these mice - the same biochemical change.

In their findings, over-expressed p11 genes, compared to the control mice, had increased mobility and more 5-HT1B receptors at the cell surface, which made possible more serotonin transmission.

[22] At the current time, a study by the National Institutes of Health Clinical Center (CC) is recruiting participants for a study that will compare levels of p11 protein in people with and without major depressive disorder (MDD) and determine whether p11 levels in patients are affected by treatment with citalopram (Celexa), a serotonin reuptake inhibitor.