Phospholipid scramblase 1 (PLSCR1) is a multiply palmitoylated, endofacial membrane protein originally identified based on its capacity to promote accelerated transbilayer phospholipid movement in response to Ca 2؉ . Recent evidence suggests that this protein also participates in cell response to various growth factors and cytokines, influencing myeloid differentiation, tumor growth, and the antiviral activity of interferon. Whereas plasma membrane PLSCR1 was shown to be required for normal recruitment and activation of Src kinase by stimulated cell surface growth factor receptors, PLSCR1 was also found to traffic into the nucleus and to tightly bind to genomic DNA, suggesting a possible additional nuclear function. We now report evidence that PLSCR1 directly binds to the 5-promoter region of the inositol 1,4,5-triphosphate receptor type 1 gene (IP3R1) to enhance expression of the receptor. Probing a CpG island genomic library with PLSCR1 as bait identified four clones with avidity for PLSCR1, including a 191-bp fragment of the IP3R1 promoter. Using electrophoretic mobility shift and transcription reporter assays, the PLSCR1-binding site in IP3R1 was mapped to residues ؊101 GTAACCATGTGGA ؊89 , and the segment spanning Met 86 -Glu 118 in PLSCR1 was identified to mediate its transcriptional activity. The significance of this interaction between PLSCR1 and IP3R1 in situ was confirmed by comparing levels of IP3R1 mRNA and protein in matched cells that either expressed or were deficient in PLSCR1. These data suggest that in addition to its role at the plasma membrane, effects of PLSCR1 on cell proliferative and maturational responses may also relate to alterations in expression of cellular IP3 receptors.
The phospholipid scramblase (PLSCR)2 gene family consists of an apparent tetrad of genes with identifiable orthologues conserved from Caenorhabditis elegans to man (1). The first identified member of this family (PLSCR1) was isolated based upon its capacity to promote Ca 2ϩ -dependent accelerated transbilayer membrane phospholipid (PL) movement, mimicking the remodeling of plasma membrane PL that is observed under conditions of injury and apoptosis (2, 3). PLSCR1 is a multiply palmitoylated, Ca 2ϩ -binding, Pro-and Cys-rich, endofacial plasma membrane protein that was shown to distribute into lipid raft domains and to be a substrate of the Abl and Src tyrosine kinases (4 -6). The exact biologic function of this protein remains controversial; although PLSCR1 mediates Ca 2ϩ -dependent transbilayer movement of PL in proteoliposomes (2, 3) and was reported to increase cell surface expression of phosphatidylserine through remodeling of plasma membrane PL in mammalian cells exposed to Ca 2ϩ ionophore and other inducers of injury or apoptosis (7-9), it has also been observed that induced elevation of PLSCR1 expression can occur without a detectable increase in PL movement between membrane leaflets, and gene deletion of PLSCR1 did not impair cell capacity to undergo this remodeling of cell surface PL (10 -12). Whereas its ro...
Background:Microsensor navigation has the potential to aid balloon sinus ostial dilation by providing real-time tracking of balloon devices within the complex anatomy of the sinonasal cavities.Objective:This feasibility study evaluated the incorporation of a new microsensor technology into a flexible guidewire for use with current instruments in balloon sinus ostial dilation.Methods:A retrospective study was conducted to include seven men and one woman (age range, 33–68 years), who underwent balloon sinus ostial dilation with flexible microsensor navigation in the operating room setting. All the procedures were performed at target sinuses with the patient under general anesthesia, in conjunction with subsequent endoscopic sinus surgery.Results:Balloon dilation was attempted at the maxillary (n = 3), frontal (n = 14), and sphenoid (n = 1) sinuses. In all the cases, the surgical navigation system displayed the flexible wire tip as it was advanced to the target sinus ostia; this visual feedback for wire position guided the balloon placement. Successful balloon dilation with assistance of flexible microsensor navigation was performed on most sinuses, except a single frontal sinus with adjacent type 2 frontal cells.Conclusion:Flexible navigation technology may be combined with balloon sinus technology to facilitate localization of instruments in the sinus anatomy. Additional optimization of both the device and software technology is warranted.
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