J Korean Diabetes Assoc.  2007 Jan;31(1):1-8. 10.4093/jkda.2007.31.1.1.

The Roles of Clusterin on Morphogenesis of Beta Cells During Pancreas Regeneration

• Hong SW
• Ranjan K
• Lee S
• Shin YJ
• Min BH
• Park IS

• KMID: 2008091
• DOI: http://doi.org/10.4093/jkda.2007.31.1.1

Abstract

Clusterin is a highly glycosylated heterodimeric glycoprotein that plays diverse biological roles in various organs. The secreted clusterin has been established as a major form of the protein that exerts diverse tissue effects. For instance, clusterin is known to act in cell protection through the actions of extra-cellular molecular chaperones. In the extracellular milieu, clusterin participates in specific interactions with a diverse array of native biological molecules including LRP-2 (Lipoprotein receptor-related protein 2, also known as gp330 or megalin), which is involved in ligand endocytosis at the surfaces of certain epithelia. Clusterin is expressed transiently in developing and differentiating endocrine pancreatic cells and might be involved in pancreas development. This transient expression of clusterin at specific time points of pancreas development and cell differentiation during pancreas regeneration implies that the protein is a regulatory factor for cytodifferentiation as well as for replication. A specific action of the clusterin in the reconstruction and remodeling of the endocrine pancreas has been demonstrated. It also strongly stimulates duct cell differentiation into insulin-secreting cells under in vitro culture conditions. Clusterin appears thus as a potent regulator of insulin cell morphogenesis.

Keyword

Beta cells; Clusterin; Development; Differentiation; Duct cells; Insulin; Regeneration

MeSH Terms

Cell Differentiation
Clusterin*
Cytoprotection
Endocytosis
Glycoproteins
Insulin
Insulin-Secreting Cells
Islets of Langerhans
Molecular Chaperones
Morphogenesis*
Pancreas*
Regeneration*
Clusterin
Glycoproteins
Insulin
Molecular Chaperones

Figure

• 

  Fig. 1 Protein structure of clusterin. ▒ Hydrophobic signal seq. (1-22). □ alternative second initiation translation site (M34); may escape glycosylation and be targeted to nucleus. █ Two coiled-coil α helices (residues 40-99 and 318-350). Human; six N-linked glycosylation sites: alpha subunit (86, 103, and 145) and beta subunit (291, 354, and 374). Rat; six N-linked glycosylation sites: alpha subunit (290, 144) and beta subunit (290, 327, 353, and 373). Amphipathic α helices (residues 173-184, 234-250, 424-441). *This figure is modified from SE Jones & C jomary/The int.

• 

  Fig. 2 Clusterin expression in normal pancreatic tissues. The protein was detected in the alpha-cells of the rat pancreatic islet at the light (A) and electron microscopic (B) levels. Clusterin was located with glucagons in the same secretory granules of the alpha cells (B).

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