title: The neonatal sarcoplasmic reticulum Ca2+-ATPase gives a clue to development and pathology in human muscles.
abstract: The sarcoplasmic/endoplasmic reticulum calcium ATPase 1 (SERCA1) has two muscle specific splice isoforms; SERCA1a in fast-type adult and SERCA1b in neonatal and regenerating skeletal muscles. At the protein level the only difference between these two isoforms is that SERCA1a has C-terminal glycine while SERCA1b has an octapeptide tail instead. This makes the generation of a SERCA1a specific antibody not feasible. The switch between the two isoforms is a hallmark of differentiation so we describe here a method based on the signal ratios of the SERCA1b specific and pan SERCA1 antibodies to estimate the SERCA1b/SERCA1a dominance on immunoblot of human muscles. Using this method we showed that unlike in mouse and rat, SERCA1b was only expressed in pre-matured infant leg and arm muscles; it was replaced by SERCA1a in more matured neonatal muscles and was completely absent in human foetal and neonatal diaphragms. Interestingly, only SERCA1a and no SERCA1b were detected in muscles of 7-12 years old boys with Duchenne, a degenerative-regenerative muscular dystrophy. However, in adult patients with myotonic dystrophy type 2 (DM2), the SERCA1b dominated over SERCA1a. Thus the human SERCA1b has a different expression pattern from that of rodents and it is associated with DM2.
authors.affiliation: Department of Biochemistry, Faculty of General Medicine, University of Szeged, Dóm tér 9, H-6720, Szeged, Hungary.
authors.forename: Magdolna
authors.initials: M
authors.lastname: Kósa
authors.forename: Kitti
authors.initials: K
authors.lastname: Brinyiczki
authors.forename: Philip
authors.initials: P
authors.lastname: van Damme
authors.forename: Nathalie
authors.initials: N
authors.lastname: Goemans
authors.forename: Károly
authors.initials: K
authors.lastname: Hancsák
authors.forename: Luca
authors.initials: L
authors.lastname: Mendler
authors.forename: Ernő
authors.initials: E
authors.lastname: Zádor
mesh_terms: D000328:Adult; D017398:Alternative Splicing; D000818:Animals; D002648:Child; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007231:Infant, Newborn; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D051379:Mice; D018482:Muscle, Skeletal / Q000201:enzymology* / Q000473:pathology; D020388:Muscular Dystrophy, Duchenne / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D009223:Myotonic Dystrophy / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D051381:Rats; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C506945:Atp2a1 protein, rat; D007527:Isoenzymes; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; C506943:ATP2A1 protein, human