Muscle glycogen synthase isoform is responsible for testicular glycogen synthesis: Glycogen overproduction induces apoptosis in male germ cells

Franz Villarroel-Espíndola, Rodrigo Maldonado, Héctor Mancilla, Karen Vander Stelt, Aníbal I. Acuña, Alejandra Covarrubias, Camila Lõpez, Constanza Angulo, Maite A. Castro, Juan Carlos Slebe, Jordi Durán, Mar García-Rocha, Joan J. Guinovart, Ilona I. Concha

Research output: Indexed journal article Articlepeer-review

21 Citations (Scopus)

Abstract

Glycogen is the main source of glucose for many biological events. However, this molecule may have other functions, including those that have deleterious effects on cells. The rate-limiting enzyme in glycogen synthesis is glycogen synthase (GS). It is encoded by two genes, GYS1, expressed in muscle (muscle glycogen synthase, MGS) and other tissues, and GYS2, primarily expressed in liver (liver glycogen synthase, LGS). Expression of GS and its activity have been widely studied in many tissues. To date, it is not clear which GS isoform is responsible for glycogen synthesis and the role of glycogen in testis. Using RT-PCR, Western blot and immunofluorescence, we have detected expression of MGS but not LGS in mice testis during development. We have also evaluated GS activity and glycogen storage at different days after birth and we show that both GS activity and levels of glycogen are higher during the first days of development. Using RT-PCR, we have also shown that malin and laforin are expressed in testis, key enzymes for regulation of GS activity. These proteins form an active complex that regulates MGS by poly-ubiquitination in both Sertoli cell and male germ cell lines. In addition, PTG overexpression in male germ cell line triggered apoptosis by caspase3 activation, proposing a proapoptotic role of glycogen in testis. These findings suggest that GS activity and glycogen synthesis in testis could be regulated and a disruption of this process may be responsible for the apoptosis and degeneration of seminiferous tubules and possible cause of infertility.

Original languageEnglish
Pages (from-to)1653-1664
Number of pages12
JournalJournal of Cellular Biochemistry
Volume114
Issue number7
DOIs
Publication statusPublished - Jul 2013
Externally publishedYes

Keywords

  • APOPTOSIS
  • GLYCOGEN
  • GLYCOGEN SYNTHASE
  • SEMINIFEROUS TUBULES
  • TESTIS

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