An unexpectedly high degree of specialization and a widespread involvement in sterol metabolism among the C. elegans putative aminophospholipid translocases.
BACKGROUND
P-type ATPases in subfamily IV are exclusively eukaryotic transmembrane proteins that have been proposed to directly translocate the aminophospholipids phosphatidylserine and phosphatidylethanolamine from the exofacial to the cytofacial monolayer of the plasma membrane. Eukaryotic genomes contain many genes encoding members of this subfamily. At present it is unclear why there are so many genes of this kind per organism or what individual roles these genes perform in organism development.


RESULTS
We have systematically investigated expression and developmental function of the six, tat-1 through 6, subfamily IV P-type ATPase genes encoded in the Caenorhabditis elegans genome. tat-5 is the only ubiquitously-expressed essential gene in the group. tat-6 is a poorly-transcribed recent duplicate of tat-5. tat-2 through 4 exhibit tissue-specific developmentally-regulated expression patterns. Strong expression of both tat-2 and tat-4 occurs in the intestine and certain other cells of the alimentary system. The two are also expressed in the uterus, during spermatogenesis and in the fully-formed spermatheca. tat-2 alone is expressed in the pharyngeal gland cells, the excretory system and a few cells of the developing vulva. The expression pattern of tat-3 is almost completely different from those of tat-2 and tat-4. tat-3 expression is detectable in the steroidogenic tissues: the hypodermis and the XXX cells, as well as in most cells of the pharynx (except gland), various tissues of the reproductive system (except uterus and spermatheca) and seam cells. Deletion of tat-1 through 4 individually interferes little or not at all with the regular progression of organism growth and development under normal conditions. However, tat-2 through 4 become essential for reproductive growth during sterol starvation.


CONCLUSIONS
tat-5 likely encodes a housekeeping protein that performs the proposed aminophospholipid translocase function routinely. Although individually dispensable, tat-1 through 4 seem to be at most only partly redundant. Expression patterns and the sterol deprivation hypersensitivity deletion phenotype of tat-2 through 4 suggest that these genes carry out subtle metabolic functions, such as fine-tuning sterol metabolism in digestive or steroidogenic tissues. These findings uncover an unexpectedly high degree of specialization and a widespread involvement in sterol metabolism among the genes encoding the putative aminophospholipid translocases.
Lyssenko
Nicholas N
NN
Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania 16802, USA. lyssenn@ccf.org
Miteva
Yana
Y
Gilroy
Simon
S
Hanna-Rose
Wendy
W
Schlegel
Robert A
RA
D000251:Adenosine Triphosphatases / Q000235:genetics; D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000196:embryology / Q000201:enzymology / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D004625:Embryo, Nonmammalian; D019143:Evolution, Molecular; D005260:Female; D018507:Gene Expression Regulation, Developmental; D008297:Male; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D005810:Multigene Family; D049294:Phospholipid Transfer Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D010802:Phylogeny; D013261:Sterols / Q000378:metabolism*; D013379:Substrate Specificity / Q000235:genetics; D014018:Tissue Distribution
D029742:Caenorhabditis elegans Proteins; D049294:Phospholipid Transfer Proteins; D013261:Sterols; D000251:Adenosine Triphosphatases; C522446:TAT-1 protein, C elegans