INVESTIGADORES
MIRANDA Silvia Esther
artículos
Título:
Progesterone induces a switch in oligosaccharyltransferase isoform expression:
Autor/es:
PRADOS MB; LA BLUNDA J; SZEKERES-BARTHO J; CARAMELO J; MIRANDA S
Revista:
IMMUNOLOGY LETTERS
Editorial:
ELSEVIER SCIENCE BV
Referencias:
Año: 2011 vol. 137 p. 28 - 37
ISSN:
0165-2478
Resumen:
The presence of additional N-glycans in the Fab region of IgG has shown to dramatically modify the
properties and functionality of these molecules including changes in antibody affinity and stability.
However, the underlying molecular mechanism responsible for the presence or absence of these glycans
remains unknown. Polypeptide N-linked glycosylation is catalyzed in the lumen of the endoplasmic
reticulum by the oligosaccharyltransferase complex. Mammalian cells can express two isoforms of the
oligosaccharyltransferase catalytic subunit (STT3-A and STT3-B), which are endowed with distinct enzymatic
properties. In this work we employed a murine hybridoma cell culture to study whether the
expression of STT3 isoforms could be modulated by progesterone, thus altering the pattern of IgG Nglycosylation.
We found that progesterone induces a switch of STT3 isoform expression, increasing IgG
N-glycosylation. These effects were dependent on the progesterone-induced blocking factor (PIBF),whose
concentration was modulated by progesterone. PIBF was previously found to be an immunomodulatory
molecule relevant for the maintenance of pregnancy. We concluded that the STT3-B/STT3-A ratio modulates
the N-glycosylation level of IgG, in agreement with previous data showing that full N-glycosylation of
polypeptides requires cooperation between both catalytic isoforms. This work provides the first evidence
that STT3 isoforms can be hormonally modulated, with marked consequences on IgG N-glycosylation.