Discovery of CLC transport proteins: cloning, structure, function and pathophysiology

Area of Science:

• Molecular Biology
• Ion Transport Physiology
• Human Genetics

Background:

• The CLC gene family encodes critical ion transporters, including chloride channels and exchangers.
• These proteins play vital roles in cellular processes and maintaining physiological balance.
• Dysfunction of CLC transporters is linked to a wide array of human diseases.

Purpose of the Study:

• To provide a historical perspective on the discovery of the Torpedo Cl(-) channel and the CLC gene family.
• To summarize the structural and functional characteristics of CLC ion transporters.
• To offer an overview of mammalian CLCs and their diverse biological roles.

Main Methods:

• Personal historical account of molecular identification.
• Review of general structural and functional features of CLC transporters.
• Overview of mammalian CLC categorization and functions.

Main Results:

• The CLC family includes plasma membrane chloride channels and vesicular chloride/proton exchangers.
• Mammalian CLCs regulate membrane excitability, transepithelial transport, and lysosomal function.
• A broad spectrum of diseases, including myotonia and neurodegeneration, result from CLC dysfunction.

Conclusions:

• The discovery of CLC-0 and the CLC gene family revealed unexpected, widespread biological importance of chloride transport.
• Understanding CLC transporter function is essential for comprehending numerous physiological processes.
• CLC-related disorders underscore the critical role of chloride transport in human health.