Journal of APPLIED BIOMEDICINE
ISSN 1214-0287 (on-line)
ISSN 1214-021X (printed)

Volume 3 (2005), No 4, p 159-165




Endoplasmic reticulum quality control and congenital pathology

Marek Michalak

Address: Marek Michalak, Department of Biochemistry, University of Alberta, 3-56 Medical Sciences Building, Edmotnon, Alberta, Canada T6G 2H7
marek.michalak@ualberta.ca

Received 6th December 2005.
Published online 12th October 2005.

Full text article (pdf)

SUMMARY
Quality control of the endoplasmic reticulum plays a critical role in protein folding, modification and modification of a secretory pathway. As endoplasmic reticulum chaperones, calreticulin and calnexin have similar substrate specificity and share several common features. Yet, surprisingly, mice bearing a disruption in the calreticulin gene die from a lesion in cardiac development and develop significant metabolic problems whereas calnexin-deficient mice are born alive with, yet not understood, neurological problems. Studies with calreticulin and calnexin gene knockout mice and calreticulin- and calnexindeficient cell lines indicate that calnexin is unable to compensate for the loss of calreticulin and conversely, calreticulin cannot compensate for the loss of calnexin. Calreticulin or calnexin deficiency or reduction in the level of ERp57 protein (ERp57 heterozygote mice) leads to development of metabolic disorders as documented by sever changes serum lipids and carbohydrates composition in these animals. These observations indicate that calreticulin, calnexin and ERp57, in addition of being involved in maturation of glycoproteins in the endoplasmic reticulum, perform other distinct functions including affecting energy metabolism.

KEY WORDS
endoplasmic reticulum; calreticulin; calnexin; chaperones; lipid metabolism


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