14.1

Aquaporins

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Water molecules are polar in nature, hence, they cannot diffuse rapidly across the non-polar lipid bilayer.

Therefore, cell membranes have special channel proteins called aquaporins that selectively transport water molecules according to the osmotic gradient.

These proteins function as tetrameric clusters, with each monomer acting as an independent water channel.

A single aquaporin channel comprises six transmembrane alpha-helices connected by five loops, of which two hydrophobic loops contain a conserved amino acid motif – Asparagine-Proline-Alanine or NPA.

The NPA residues form a constricted site that confines the water molecules into a single file as they pass through the channel.

Additionally, repulsion from the hydrophobic walls of the channel accelerates the movement of the water molecules.

While passing through the constricted site, the oxygen atoms interact with the asparagine residues of the NPA motif, interrupting the hydrogen-bonded bridges between the water molecules that would have otherwise allowed protons to hop in and pass through the channel.

Disruption of the hydrogen-bonded network prevents proton movement, making the aquaporin selectively permeable to water.

Overview

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Aquaporins or AQPs are a family of integral membrane proteins whose primary function is to transport water, while some called aquaglyceroporins also transport glycerol. In addition, aquaporins have also been suspected to be involved in transporting volatile substances, such as carbon dioxide and ammonia, across membranes. Such AQPs that act as gas channels are often highly expressed in cells involved in the gaseous exchange, such as red blood cells, epithelial cells, and pulmonary capillaries.

In contrast, the water selective AQPs are widely expressed and are crucial in water-transporting organs and tissues such as the kidneys, the exocrine glands, and the central nervous system. Nonetheless, these channels are also found in the lungs, the skeletal muscles, and the gastrointestinal organs, although they may not be functionally significant. While the water-selective AQPs are essential for cell migration, neuroexcitation, and epithelial fluid transport, the aquaglyceroporins are involved in adipocyte metabolism, skin hydration, and cell proliferation.

Due to their involvement in physiological functions, overexpression or deficiency of AQPs have been associated with several human diseases, including renal dysfunction, epilepsy, skin disease, cancer, neurological disorder, and cardiac ailments. For example, mutations in human AQP1 or AQP2 can result in defective urine concentrating processes. In rare instances, loss of function mutation in AQP2 leads to non-X-linked nephrotic diabetes insipidus or NDI, a condition characterized by unusually high urine output. Similarly, mutations in the major intrinsic protein of AQP (AQP0) of the eye lens can lead to congenital cataracts. Due to their significance in various human illnesses, many scientists have shown active interest in targeting AQPs for therapy.

Although most aquaporins function as open channels, some of them, especially in plants, have evolved to have a gated mechanism. Such aquaporins close down in response to harsh conditions of the environment, such as drought, stress, or flooding, under which the exchange of water can be harmful to the organism.

Transcript

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