Proteoglycan

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Overview

Structure of aggrecan, a major proteoglycan in cartilage.

Proteoglycans are a major component of the extracellular matrix (ECM) in animals, providing structural support to tissues and influencing various cellular processes. They are composed of a core protein covalently attached to one or more glycosaminoglycan (GAG) chains. These macromolecules are highly diverse in structure and function, playing critical roles in the biomechanics of tissues, cell signaling, and cell adhesion.

Structure

Proteoglycans consist of a core protein to which GAG chains are attached. The GAG chains are long, linear carbohydrate polymers that are negatively charged due to the presence of sulfate and uronic acid groups. This negative charge allows proteoglycans to attract water and cations, contributing to the turgor pressure and resilience of tissues.

Core Protein

The core protein of a proteoglycan determines its specific function and interaction with other ECM components. Different types of proteoglycans have distinct core proteins, which can vary in size and domain structure.

Glycosaminoglycan Chains

GAG chains are composed of repeating disaccharide units. Common types of GAGs include chondroitin sulfate, dermatan sulfate, heparan sulfate, keratan sulfate, and hyaluronic acid. The specific composition and length of GAG chains influence the properties and functions of the proteoglycan.

Function

Proteoglycans serve multiple functions in the body:

  • Structural Support: They provide mechanical support to tissues such as cartilage, where they help resist compressive forces.
  • Cell Signaling: Proteoglycans interact with growth factors and cytokines, modulating their activity and availability to cells.
  • Cell Adhesion: They play a role in cell-matrix interactions, influencing cell adhesion, migration, and proliferation.
  • Filtration: In the glomerular basement membrane of the kidney, proteoglycans contribute to the filtration barrier.

Types of Proteoglycans

Proteoglycans are classified based on their location and function:

  • Aggrecan: Found in cartilage, aggrecan is a large proteoglycan that provides compressive strength.
  • Versican: Present in many tissues, versican is involved in cell adhesion and migration.
  • Syndecans: These are transmembrane proteoglycans that participate in cell signaling and adhesion.
  • Perlecan: Located in basement membranes, perlecan is important for filtration and structural integrity.

Clinical Significance

Abnormalities in proteoglycan structure or function can lead to various diseases. For example, mutations affecting aggrecan can result in osteoarthritis and spondyloepiphyseal dysplasia. Proteoglycans are also involved in the progression of cancer, as they can influence tumor growth and metastasis.

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Contributors: Prab R. Tumpati, MD