The structure of the Ca2+-ATPase of sarcoplasmic reticulum.

Abstract

In this article the morphology of sarcoplasmic reticulum, classification of Ca(2+)-ATPase (SERCA) isoenzymes presented in this membrane system, as well as their topology will be reviewed. The focus is on the structure and interactions of Ca(2+)-ATPase determined by electron and X-ray crystallography, lamellar X-ray and neutron diffraction analysis of the profile structure of Ca(2+)-ATPase in sarcoplasmic reticulum multilayers. In addition, targeting of the Ca(2+)-ATPase to the sarcoplasmic reticulum is discussed.

Novel mutations in two families with Darier's disease

“…The transmembrane sectors contain Ca +2 binding sites and channels for transporting it into the ER. 12 Alternative splicing of the ATP2A2 gene's product gives rise to two isoforms: SERCA2a and SERCA2b. The latter has an extended C-terminal region, 13 and is expressed mainly in smooth muscle and nonmuscle tissues, including keratinocytes.…”

“…The latter has an extended C-terminal region, 13 and is expressed mainly in smooth muscle and nonmuscle tissues, including keratinocytes. 7,12 Experiments with specific inhibitors of the SERCA pumps point to the significance of the Ca +2 ATPase activity in the recruitment and trafficking of desmosomal proteins. Thus, loss or aberrant function can result in defective epidermal desmosomes' assembly, leading to cell detachment, acantholysis and dyskeratosis typical of DD.…”

Calcium pumps and keratinocytes: lessons from Darier's disease and Hailey-Hailey disease

“…The active site for ATP hydrolysis is formed in the phosphorylation and nucleotide binding domains. The transmembrane domain containing Ca 2+ binding sites forms the channel for transport of Ca 2+ into the ER 37 …”

“…Three genes, ATP2A1 , ATP2A2 and ATP2A3 , encode three types of SERCA protein, SERCA1, SERCA2 and SERCA3, and alternative splicing of the primary transcripts gives rise to at least nine SERCA isoforms with different functions 33–37 …”

“…SERCA1a is expressed predominantly in adult fast‐twitch muscle and SERCA1b is the alternatively spliced neonatal form of SERCA1. The SERCA2a isoform is found mainly in adult slow‐twitch cardiac and skeletal muscle, as well as neonatal muscle 37,38 . SERCA2a is expressed at a much lower level in nonmuscle cells including keratinocytes 16 .…”