A proteomic study of calpain-3 and its involvement in limb girdle muscular dystrophy type 2a.

Cell Calcium
Ilenia BertipagliaErnesto Carafoli

Abstract

Limb-girdle muscular dystrophy type 2A is an autosomal recessive disorder generated by inactivating mutations in the gene coding for the muscle specific protease calpain-3. It is mainly expressed in skeletal muscle as a monomeric multidomain protein characterized by three unique insertion sequences (NS, IS1, IS2). It is unstable, and undergoes very rapid autolysis in solution, therefore, its heterologous expression and purification have been difficult. So far, calpain-3 substrates have been only identified in vitro and with indirect approaches. We have therefore decided to perform a comprehensive study of the substrates of the protease by comparing the 2D electrophoretic profile of myotubes from obtained from calpain-3 knockout and wild type mice. Digestion of differentially expressed spots was followed by mass spectrometry analysis. We could identify 16 proteins which differed in knockout and wild type mice. Among them: desmin, nestin, spectrin and PDLIM1 were of particular interest. In vitro experiments have then revealed that only PDLIM1 is cleaved directly by the protease, and that a fragment of about 8 kDa is released from the C-terminal portion of the protein.

References

Apr 25, 1988·FEBS Letters·L RappaportM Fardeau
Mar 8, 1995·Biochemical and Biophysical Research Communications·T YoshizawaK Suzuki
Dec 6, 1996·The Journal of Biological Chemistry·S KurodaU Kikkawa
Feb 18, 1999·Journal of Cellular Biochemistry·M KotakaM M Waye
Feb 27, 1999·Current Opinion in Cell Biology·C C GregorioS Labeit
Jun 22, 2000·Journal of Cellular Biochemistry·M KotakaM M Waye
May 1, 2001·Journal of Biochemistry·H Sorimachi, K Suzuki
Feb 21, 2002·Cellular and Molecular Life Sciences : CMLS·L G J NijtmansP J Coates
Jul 5, 2003·Physiological Reviews·Darrell E GollJinyang Cong
Nov 5, 2003·The Journal of Biological Chemistry·Yasuko OnoHiroyuki Sorimachi
Feb 28, 2004·The Journal of Biological Chemistry·Peter TompaPeter Friedrich
Jun 3, 2004·Journal of Cell Science·Luguo SunZhenguo Wu
Jun 3, 2004·Electrophoresis·Giovanni CandianoPier Giorgio Righetti
Nov 3, 2004·Nature Reviews. Molecular Cell Biology·Julie L Kadrmas, Mary C Beckerle
Mar 15, 2006·Biochemistry·Beatriz E García DíazPeter L Davies
Aug 4, 2006·The FEBS Journal·Stéphanie DuguezIsabelle Richard
Oct 30, 2007·Biochemical and Biophysical Research Communications·Naoaki TamuraKohji Sato

❮ Previous
Next ❯

Citations

May 1, 2012·Cardiovascular Research·Hiroyuki Sorimachi, Yasuko Ono
Sep 13, 2015·Biochimie·Yasuko OnoHiroyuki Sorimachi
Sep 25, 2014·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Koichi OjimaHiroyuki Sorimachi
Sep 8, 2012·Circulation Research·Shuchi GuptaBernhard Nieswandt

❮ Previous
Next ❯

Related Concepts

Related Feeds

Calcium & Bioenergetics

Bioenergetic processes, including cellular respiration and photosynthesis, concern the transformation of energy by cells. Here is the latest research on the role of calcium in bioenergetics.

Related Papers

The New England Journal of Medicine
Mayana Zatz, Alessandra Starling
Biochemical and Biophysical Research Communications
Anuradhaa WaghrayKevin K W Wang
American Journal of Physiology. Cell Physiology
David D ArringtonRick G Schnellmann
Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism
Matthew B Bevers, Robert W Neumar
Journal of Chemical Neuroanatomy
Norbert KönigY Benyamin
© 2022 Meta ULC. All rights reserved