Identification of a novel mouse P4-ATPase family member highly expressed during spermatogenesis.
P4-ATPases are transmembrane proteins unique to eukaryotes that play a fundamental role in vesicular transport. They have been proposed to act as phospholipid flippases thereby regulating lipid topology in cellular membranes. We cloned and characterized a novel murine P4-ATPase that is specifically expressed in testis, and named it FetA (flippase expressed in testis splicing form A). When expressed in Saccharomyces cerevisiae, FetA localizes partially to the plasma membrane resulting in increased internalization of NBD-labeled phosphatidylethanolamine and phosphatidylcholine, supporting a role for FetA in the inward lipid translocation across cellular membranes. In mouse testis, FetA protein is detected in gamete cells, from pachytene spermatocytes to mature sperms, and its intracellular localization is tightly related with acrosome formation, a process that involves intensive intracellular vesicle formation and fusion. Furthermore, loss-of-function of FetA by RNA interference in mastocytoma P815 cells profoundly perturbs the structural organization of the Golgi complex and causes loss of constitutive secretion at lower temperature. Our findings point to an essential role of FetA in Golgi morphology and secretory function, suggesting a crucial role for this novel murine P4-ATPase in spermatogenesis.
Xu
Peng
P
Laboratory of Molecular Cell Biology, Key Laboratory of Stem Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of Chinese Academy of Sciences, China.
Okkeri
Juha
J
Hanisch
Susanne
S
Hu
Rui-Ying
RY
Xu
Qin
Q
Pomorski
Thomas Günther
TG
Ding
Xiao-Yan
XY
D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D045744:Cell Line, Tumor; D004705:Endocytosis; D017353:Gene Deletion; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006056:Golgi Apparatus / Q000201:enzymology / Q000473:pathology / Q000648:ultrastructure; D050356:Lipid Metabolism; D008297:Male; D034801:Mastocytoma / Q000201:enzymology / Q000473:pathology; D051379:Mice; D008969:Molecular Sequence Data; D009928:Organ Specificity; D010802:Phylogeny; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D016415:Sequence Alignment; D013091:Spermatogenesis / Q000235:genetics; D013737:Testis / Q000166:cytology / Q000196:embryology / Q000201:enzymology
D012333:RNA, Messenger; D000251:Adenosine Triphosphatases