Endoplasmic reticulum quality control and congenital pathology
Title:
Endoplasmic reticulum quality control and congenital pathology
Author:
Marek Michalak
Appeared in:
Journal of applied biomedicine
Paging:
Volume 3 (2005) nr. 4 pages 159-165
Year:
2005
Contents:
Quality control of the endoplasmic reticulum plays a critical role in protein folding, modification andmodification of a secretory pathway. As endoplasmic reticulum chaperones, calreticulin and calnexinhave similar substrate specificity and share several common features. Yet, surprisingly, mice bearing adisruption in the calreticulin gene die from a lesion in cardiac development and develop significantmetabolic problems whereas calnexin-deficient mice are born alive with, yet not understood, neurologicalproblems. Studies with calreticulin and calnexin gene knockout mice and calreticulin- and calnexindeficientcell lines indicate that calnexin is unable to compensate for the loss of calreticulin andconversely, calreticulin cannot compensate for the loss of calnexin. Calreticulin or calnexin deficiency orreduction in the level of ERp57 protein (ERp57 heterozygote mice) leads to development of metabolicdisorders 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 inmaturation of glycoproteins in the endoplasmic reticulum, perform other distinct functions includingaffecting energy metabolism.
Journal description