Enhanced response of T lymphocytes from Pgap3 knockout mouse

Insight into roles of fatty acid remodeling of GPI anchored proteins

Hidekazu Murakami, Yetao Wang, Hidetoshi Hasuwa, Yusuke Maeda, Taroh Kinoshita, Yoshiko Murakami

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Glycosylphosphatidylinositol (GPI) is a complex glycolipid that serves as a membrane anchor for many cell-surface proteins, such as Thy-1 and CD48. GPI-anchored proteins (GPI-APs) play important roles in many biological processes, such as signal transduction and cell-cell interaction, through their association with lipid rafts. Fatty acid remodeling of GPI-APs in the Golgi apparatus is required for their efficient association with lipid rafts, i.e., the unsaturated fatty acid at the sn-2 position of the PI moiety is exchanged for the saturated fatty acid by PGAP2 and PGAP3. To investigate the immunological role of the fatty acid remodeling of GPI-APs, we generated a Pgap3 knockout mouse. In this mouse, GPI-APs are expressed on the cell surface without fatty acid remodeling, and fail to associate with lipid rafts. Male Pgap3 knockout mice were born alive at a ratio lower than expected from Mendel's law, whereas the number of female mice followed Mendel's law. All mice exhibited growth retardation and abnormal reflexes such as limb grasping. We focused T cell function in these mice and found that T cell development in the absence of Pgap3 was normal. However, the response of T cells was enhanced in Pgap3 knockout mice in both in vitro and in vivo studies, including alloreactive response, antigen-specific immune response, and experimental autoimmune encephalomyelitis. Cross-linking of Thy-1 in wild-type cells inhibited the signal transduced by the T cell receptor (TCR), whereas cross-linking of Thy-1 in Pgap3 knockout cells enhanced the TCR signal. These results suggest that GPI-APs localized in lipid rafts may modulate signaling through the TCR.

Original languageEnglish
Pages (from-to)1235-1241
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume417
Issue number4
DOIs
Publication statusPublished - 2012 Jan 27
Externally publishedYes

Fingerprint

Glycosylphosphatidylinositols
T-cells
Knockout Mice
Fatty Acids
T-Lymphocytes
T-Cell Antigen Receptor
Lipids
Proteins
Histocompatibility Antigens Class II
Association reactions
Biological Phenomena
Abnormal Reflexes
Signal transduction
Autoimmune Experimental Encephalomyelitis
Glycolipids
Golgi Apparatus
Anchors
Unsaturated Fatty Acids
Cell Communication
Signal Transduction

Keywords

  • Glycosylphosphatidylinositol-anchor
  • Lipid raft
  • Lipid remodeling
  • Pgap3
  • T cell signal
  • Thy-1

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

Cite this

Enhanced response of T lymphocytes from Pgap3 knockout mouse : Insight into roles of fatty acid remodeling of GPI anchored proteins. / Murakami, Hidekazu; Wang, Yetao; Hasuwa, Hidetoshi; Maeda, Yusuke; Kinoshita, Taroh; Murakami, Yoshiko.

In: Biochemical and Biophysical Research Communications, Vol. 417, No. 4, 27.01.2012, p. 1235-1241.

Research output: Contribution to journalArticle

Murakami, Hidekazu ; Wang, Yetao ; Hasuwa, Hidetoshi ; Maeda, Yusuke ; Kinoshita, Taroh ; Murakami, Yoshiko. / Enhanced response of T lymphocytes from Pgap3 knockout mouse : Insight into roles of fatty acid remodeling of GPI anchored proteins. In: Biochemical and Biophysical Research Communications. 2012 ; Vol. 417, No. 4. pp. 1235-1241.
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