Impaired glycogen accumulation in the RGL, glycogen associated subunit of PPl, knockout mice

Yoichi Suzuki, Carita Larrér, Hong Zhang, David A. Williams, Anna A. Delpaoli-Roach

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Abstract

I he protein phosphatase I'lMG has been implicated in the control of glycogen metabolism. 1 ho enzyme is composed of a catalytic. CI, and a regulatory. RGLsubunit. RGL targets the enzyme to glycogen. where it may control the activity of glycogen metabolizing enzymes, and to membranes, where it may affect phosphorylation of phospholamban. To assess the physiological rolo of P P iG. we have disrupted the R(7/, gene in mice. Knockout mice were generated by replacing oxun 1 with the neoniycin gene. Animals deficient in RC,-/, show no apparent morphological or developmental defects. The RGL protein is absent from the skeletal and cardiac muscle of null mutants and only 50 of the wild type is present in the hetero/ygotes. Both Cl protein and activity an1 decreased by 50% the RGLdeficient mice, indicating that expression of the regulatorv snbunit is required for stabilization of Cl. In skeletal muscle, but not in heart, the giycogen synthase -/+ G-i-P activity ratio, an indication of pliosphorylation sîate. is reduced from 0.3 in the wild type to 0.07 in the null mutant Rr;/, mice and to 0.17 it thr. hétérozygotes. Conversely, the activity state of phosphorylase appears to be increased in skeletal but not in cardiac muscle. Glycogen accumulation is reduced by 90% in both tissues. These results stiongly indicate thai RGL, and thus, PPlG is required for glycogtMi accumulation. K'lrthertnore. these findings suggest that glycogen metabolism may be differentiailly regulated in skeetal and cardiac muscles.

Original languageEnglish
Pages (from-to)A1297
JournalFASEB Journal
Volume12
Issue number8
Publication statusPublished - 1998 Dec 1

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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    Suzuki, Y., Larrér, C., Zhang, H., Williams, D. A., & Delpaoli-Roach, A. A. (1998). Impaired glycogen accumulation in the RGL, glycogen associated subunit of PPl, knockout mice. FASEB Journal, 12(8), A1297.