PMID- 18426892
OWN - NLM
STAT- MEDLINE
DCOM- 20080708
LR  - 20211020
IS  - 1098-5522 (Electronic)
IS  - 0019-9567 (Print)
IS  - 0019-9567 (Linking)
VI  - 76
IP  - 7
DP  - 2008 Jul
TI  - Novel role of sphingolipid synthesis genes in regulating giardial encystation.
PG  - 2939-49
LID - 10.1128/IAI.00116-08 [doi]
AB  - Although encystation (cyst formation) is important for the survival of Giardia 
      lamblia outside its human host, the molecular events that prompt encystation have 
      not been fully elucidated. Here, we demonstrate that sphingolipids (SLs), which 
      are important for the growth and differentiation of many eukaryotes, play key 
      roles in giardial encystation. Transcriptional analyses showed that only three 
      genes in the SL biosynthesis pathways are expressed and transcribed 
      differentially in nonencysting and encysting Giardia trophozoites. While the 
      putative homologues of giardial serine palmitoyltransferase (gSPT) subunit genes 
      (gspt-1 and -2) are differentially expressed in nonencysting and encysting 
      trophozoites, the giardial ceramide glucosyltransferase 1 gene (gglct-1) is 
      transcribed only in encysting cells. l-Cycloserine, an inhibitor of gSPT, 
      inhibited the endocytosis and endoplasmic reticulum/perinuclear targeting of 
      bodipy-ceramide in trophozoites, and this could be reversed by 3-ketosphinganine. 
      On the other hand, D-threo-1-phenyl-2-palmitoylamino-3-morpholino-1-propanol 
      (PPMP), an inhibitor of glucosylceramide synthesis, blocked karyokinesis and 
      reduced cyst production in culture. PPMP also altered the expression of cyst wall 
      protein transcripts in encysting cells. Phylogenetic analyses revealed that the 
      gspt genes are paralogs derived from an ancestral spt sequence that underwent 
      gene duplication early in eukaryotic history. This ancestral sequence, in turn, 
      was probably derived from prokaryotic aminoacyl transferases. In contrast, 
      gglct-1 is found in both prokaryotes and eukaryotes without any evidence of gene 
      duplication. These studies indicate that SL synthesis genes are involved in key 
      events in giardial biology and could serve as potential targets for developing 
      new therapies against giardiasis.
FAU - Hernandez, Yunuen
AU  - Hernandez Y
AD  - Department of Biological Sciences, University of Texas at El Paso, 500 W. 
      University Avenue, El Paso, TX 79968-0519, USA.
FAU - Shpak, Max
AU  - Shpak M
FAU - Duarte, Trevor T
AU  - Duarte TT
FAU - Mendez, Tavis L
AU  - Mendez TL
FAU - Maldonado, Rosa A
AU  - Maldonado RA
FAU - Roychowdhury, Sukla
AU  - Roychowdhury S
FAU - Rodrigues, Marcio L
AU  - Rodrigues ML
FAU - Das, Siddhartha
AU  - Das S
LA  - eng
SI  - RefSeq/XP_767155
SI  - RefSeq/XP_767432
SI  - RefSeq/XP_779228
GR  - S06 GM 008012/GM/NIGMS NIH HHS/United States
GR  - G12 RR008124/RR/NCRR NIH HHS/United States
GR  - 5G112RR08124/RR/NCRR NIH HHS/United States
GR  - 2R25GM069621/GM/NIGMS NIH HHS/United States
GR  - G12 MD007592/MD/NIMHD NIH HHS/United States
GR  - S06 GM008012/GM/NIGMS NIH HHS/United States
GR  - R25 GM069621/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20080421
PL  - United States
TA  - Infect Immun
JT  - Infection and immunity
JID - 0246127
RN  - 0 (Ceramides)
RN  - 0 (DNA, Protozoan)
RN  - 0 (Protozoan Proteins)
RN  - 0 (Sphingolipids)
RN  - EC 2.4.1.- (Glucosyltransferases)
RN  - EC 2.4.1.80 (ceramide glucosyltransferase)
SB  - IM
MH  - Animals
MH  - Ceramides/metabolism
MH  - DNA, Protozoan/analysis
MH  - *Gene Expression Regulation
MH  - Genes, Protozoan
MH  - Giardia lamblia/genetics/metabolism/*physiology
MH  - Glucosyltransferases/genetics/metabolism
MH  - Molecular Sequence Data
MH  - Phylogeny
MH  - Protozoan Proteins/genetics/*metabolism
MH  - Sequence Analysis, DNA
MH  - Sphingolipids/*biosynthesis
MH  - Trophozoites/growth & development/metabolism
PMC - PMC2446683
EDAT- 2008/04/23 09:00
MHDA- 2008/07/09 09:00
PMCR- 2008/11/01
CRDT- 2008/04/23 09:00
PHST- 2008/04/23 09:00 [pubmed]
PHST- 2008/07/09 09:00 [medline]
PHST- 2008/04/23 09:00 [entrez]
PHST- 2008/11/01 00:00 [pmc-release]
AID - IAI.00116-08 [pii]
AID - 0116-08 [pii]
AID - 10.1128/IAI.00116-08 [doi]
PST - ppublish
SO  - Infect Immun. 2008 Jul;76(7):2939-49. doi: 10.1128/IAI.00116-08. Epub 2008 Apr 
      21.