Cytoplasmic domain of P-selectin (CD62) contains the signal for sorting into the regulated secretory pathway.

Disdier, Magali; Morrissey, James H.; Fugate, Robert D.; Bainton, Dorothy F.; McEver, Rodger P.

doi:10.1091/mbc.3.3.309

Cited by 155 publications

(117 citation statements)

References 46 publications

(49 reference statements)

Supporting

Mentioning

111

Contrasting

Unclassified

Order By: Relevance

“…Fig. 2B shows that wt HRP-P-selectin peaks in the same fractions (15)(16)(17)(18)(19) that contain the marker ␤-hexosaminidase in resting cells and that this compartment also responds to stimulation of the cells caused by aggregation of the Fc⑀RI for 25 min. Thus HRP-P-selectin is targeted to the functionally active secretory lysosome.…”

Section: Resultsmentioning

confidence: 99%

P-selectin Targeting to Secretory Lysosomes of Rbl-2H3 Cells

Kaur

Cutler

2002

Journal of Biological Chemistry

View full text Add to dashboard Cite

The biogenesis of secretory lysosomes, which combine characteristics of both lysosomes and secretory granules, is currently of high interest. In particular, it is not clear whether delivery of membrane proteins to the secretory lysosome requires lysosomal, secretory granule, or some novel targeting determinants. Heterologous expression of P-selectin has established that this membrane protein contains targeting signals for both secretory granules and lysosomes. P-selectin is therefore an ideal probe with which to determine the signals required for targeting to secretory lysosomes. We have exploited subcellular fractionation and immunofluorescence microscopy to monitor targeting of transiently expressed wild-type and mutant horseradish peroxidase (HRP)-P-selectin chimeras to secretory lysosomes of Rbl-2H3 cells. The exposure of the HRP chimeras to intracellular proteolysis was also determined as a third monitor of secretory lysosome targeting. Our data show that HRP-P-selectin accumulates in secretory lysosomes of Rbl-2H3 cells using those cytoplasmic sequences previously found to be sufficient for targeting to conventional lysosomes. This work highlights the similar sorting signals used for targeting of membrane proteins to conventional lysosomes and secretory lysosomes.

show abstract

Section: Resultsmentioning

confidence: 99%

P-selectin Targeting to Secretory Lysosomes of Rbl-2H3 Cells

Kaur

Cutler

2002

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…In contrast, transfection of P-selectin cDNA leads to its storage in the endogenous granules of the transfected cell lines (28,29). Even though this result indicates that P-selectin contains an independent sorting signal now identified in the cytoplasmic tail (30), it also indicates that P-selectin needs some pre-existing storage granules to be directed to, as recently confirmed in transfected cells (31). Immunolocalization of P-selectin with the use of confocal microscopy showed that in resting vWf Ϫ͞Ϫ endothelial cells, P-selectin is found in a reduced number of small vesicles, compared with vWf ϩ͞ϩ cells (Fig.…”

Section: Discussionmentioning

confidence: 96%

Defect in regulated secretion of P-selectin affects leukocyte recruitment in von Willebrand factor-deficient mice

Denis

André

Saffaripour

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

156

145

View full text Add to dashboard Cite

Stimulation of endothelial cells by various inflammatory mediators leads to release of Weibel-Palade bodies and therefore to exocytosis of both P-selectin (adhesion receptor for leukocytes) and von Willebrand factor (vWf) (platelet ligand). The potential role of vWf in leukocyte recruitment was investigated with the use of vWfdeficient mice. We report a strong reduction of leukocyte rolling in venules of vWf-deficient mice. Similarly, vWf deficiency led to a decrease in neutrophil recruitment in a cytokine-induced meningitis model as well as in early skin wounds. In all instances with an antibody that preferentially recognizes plasma membrane P-selectin, we observed a dramatic reduction in P-selectin expression at the cell surface of vWf-deficient endothelium. With confocal microscopy, we found that the typical rodlike shape of the WeibelPalade body is missing in vWf ؊͞؊ endothelial cells and that part of the P-selectin content in the vWf ؊͞؊ cells colocalized with LAMP-1, a lysosomal marker. However, intracellular P-selectin levels were similar in tumor necrosis factor ␣-and lipopolysaccharide-activated cells of both genotypes. We conclude that the absence of vWf, as found in severe von Willebrand disease, leads to a defect in Weibel-Palade body formation. This defect results in decreased P-selectin translocation to the cell surface and reduced leukocyte recruitment in early phases of inflammation.

show abstract

“…The sorting mechanism for integral membrane proteins of the granule has also been studied in this way, and appears to be quite different from that for soluble proteins. Thus P-selectin, a transmembrane protein localized to granules in endothelial cells, is directed to granules in AtT20 cells by virtue of a cytoplasmic domain [136]. The second approach for identifying domains implicated in protein sorting to the regulated pathway depends upon the comparison of sequences and postulated ordered three-dimensional structures of all proteins destined for this pathway.…”

Section: Possible Mechanisms For Sorting Of Regulated Proteins In Thementioning

confidence: 99%