Anat Cell Biol.  2011 Sep;44(3):169-175. 10.5115/acb.2011.44.3.169.

Proapoptotic role of nuclear clusterin in brain

Affiliations
  • 1Department of Anatomy and Neurobiology, Medical Research Center for Neural Dysfunction, Institute of Health Science, Gyeongsang National University School of Medicine, Jinju, Korea. choiws@gnu.ac.kr

Abstract

Clusterin (CLU) is a multifunctional glycoprotein that has secretory and nuclear isoforms. The two isoforms are known to play opposite roles in cell survival/death. In this review, we summarize recent progress on the pro-apoptotic function of nuclear CLU in vitro and in vivo and discuss previous reports on the role of CLU in brain damage and neurodegeneration.

Keyword

Clusterin; Apoptosis; Brain

MeSH Terms

Apoptosis
Brain
Clusterin
Glycoproteins
Protein Isoforms
Clusterin
Glycoproteins
Protein Isoforms

Figure

  • Fig. 1 Structure of nuclear clusterin (nCLU). (A) Schematic view of the CLU protein. The human CLU gene is located on chromosome 8 and consists of nine exons. The secretory CLU transcript starts with the first ATG (amino acid [a.a.] residue 1) and that of nCLU starts with the second ATG (a.a. 34). The CLU protein has two coiled coil (CC) domains and the putative Bcl-2 homology 3 (BH3) motif (a.a. 316-336) is in CC2. LP, leader peptide. (B) Sequence homolog y of BH3 motifs among BH3-only proteins. The core BH3 sequences are underlined, and the highly conserved arginine (L) is in red. The BH3 motif is responsible for binding the anti-apoptotic Bcl-2 family, such as Bcl-2 and Bcl-XL.

  • Fig. 2 Colocalization of clusterin (CLU) and Bcl-XL in the thalamus of the developing brain following ethanol treatment. Seven-day-old rats were subcutaneously injected with 6 g/kg of ethanol. After the designated times, they were sacrificed and perfused. Immunohistochemistry revealed that CLU expression was upregulated (left column) and colocalized with Bcl-XL (arrows) in the thalamus. The middle column show Bcl-XL expression, and the right column show merged images. E, ethanol treatment (×400).


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